Fc epsilon receptor (FCERI) signaling (Homo sapiens)

From WikiPathways

Revision as of 11:25, 10 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
24, 7011154, 79, 8880, 8410858, 1101610, 22112, 115, 12411, 38, 83, 10268, 104840, 66, 89, 113, 12523, 28, 34, 1145, 31, 1051, 25, 26, 67, 1221413, 9321, 49, 51, 11929, 6399, 103, 11850, 102, 10642, 73, 120, 12155, 62, 63, 77, 8712, 5739, 41, 906, 7, 15, 18, 32...9, 1720, 69, 10081, 11142, 73, 120, 1212, 27, 5282, 107, 11954, 95, 11774, 9434, 11745, 786119, 71, 1096475, 9218563, 37, 47, 866553, 7643, 8536, 46, 72, 973033, 60, 10148, 1164, 28, 123GRB2SOS1 RasGRPsDAGCa2+ GADSSLP76 CBM oligomeroligo-K63-poly Ub-TRAF6 oligomer GRB2SOS1 CBM oligomerTRAF6 oligomer PLC gamma1/2 p-SHC1GRB2SOS CBM oligomeroligo-K63-poly Ub-TRAF6 oligomer FCERI Immunoglobulin Lambda Light Chain p-VAV Ig Kappa Light Chain V Region GRB2SOS1 FCERIIgE Ig Heavy Chain V Region DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6activated TAK1 complex MALT1 trimer p-SHC1GRB2SOS PI3K-regulatory subunit nucleoplasmp-2S-cJUNp-2S,2T-cFOS IgE p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG p-SHC1GRB2SOS CBM oligomerTRAF6 p-SHC1GRB2SOS IP3 receptors PLC gamma1/2 Active Calmodulin PDK1PIP2,PIP3 GRB2SOS1 VAV p-CARMA1 oligomerBCL10MALT1 DAGp-5Y-PKC-thetap-S552,S645-CARMA1 CaN-catalytic alpha/beta chains CaN alpha regulatoryCa2+ Ig Lambda C region Immunoglobulin Kappa Light Chain p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAV Ubc13UBE2V1 p-5Y-LATp-SHC1GRB2SOS1 CaN catalytic alpha/betaZn++Fe3+ Ubc13UBE2V1 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76p-PLCG p-5Y-PKC-thetaDAG Ig Heavy Chain V Region Calcineurin alpha regulatory subunitCalcium p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG Ig Antibody Light Chain GRB2SOS1 p-5Y-LATp-SHC1GRB2SOS1 p-10Y-NTALp-SHC1GRB2SOS p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-BTK/p-2Y-ITKPIP3 RAC1-GDP PI3K-regulatory subunit GRB2SOS1 DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6 Ig Kappa Light Chain V Region PPP3CA/BFe3+Zn2+ TAB1TAB2/TAB3TAK1 p-5Y-LATp-SHC1GRB2SOS1GADSSLP76 BCL10MALT1 PPP3CA/B PLC gamma1/2 FCERIIgEallergin aggregate Ig Lambda C region Immunoglobulin Kappa Light Chain DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6 GRB2SOS1 CBM oligomer Calcineurin alpha regulatory subunitCalcium p-VAV p-SHC1GRB2SOS VAV p-5Y-PKC-thetaDAG p-SHC1GRB2SOS PAK2 dimer Ig Kappa Light Chain V Region IgE Heavy Chain GADSp-Y113,Y128,Y145-SLP-76 Ub-TRAF6 trimer bound to CBM complex Active Calmodulin p-5Y-LATp-SHC1GRB2SOS1 PPP3CA/B Ig Lamda Light Chain V Region Clustered pLYNp-FCERIIgEallerginp-6Y-SYK DAGp-5Y-PKC-thetaCBM oligomerTRAF6 p-S177,S181-IKKBIKKApUb-NEMO PI3K TAB2/3 Ig Antibody Light Chain GRB2SOS1 GRB2SOS1 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG Calcineurin p21 RASGTP p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTP p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTPPAK dimer IgE Heavy Chain VAV IP3 receptor homotetramer p-5Y-LATp-SHC1GRB2SOS1 IKKAIKKBNEMO p-10Y-NTALp-SHC1GRB2SOSGAB2 endoplasmic reticulum lumenIg Kappa Light Chain V Region PDK1PIP2,PIP3 p-5Y-LATp-SHC1GRB2SOS1 IgE p-5Y-PKC-thetaDAG NF-kB complex Ig Antibody Light Chain GRB2SOS1 p-5Y-PKC-thetaDAG CalcineurinCalmodulin PPP3CA/BCalmodulin p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG BCL10 oligomerMALT1 oligomerTRAF6 p-VAV NFATCaNCaM p21 RASGDP p-5Y-PKC-thetaDAG p-LYNp-FCERIIgE aggregate VAV p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAV PAK1 dimer p-5Y-LATp-SHC1GRB2SOS1GADSSLP76PLCG p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-TEC kinases Immunoglobulin Lambda Light Chain Ig Lambda C region PPP3CA/BCalmodulin IP3 receptors PPP3CA/BFe3+Zn2+ NF-kB complex Immunoglobulin Lambda Light Chain Dephosphorylated NFAT p-5Y-LATp-SHC1GRB2SOS1 p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTP GRB2SOS1 Ig Lambda C region PLC gamma1/2 DAGp-5Y-PKC-thetaCBM oligomerTRAF6 oligomer p-5Y-LATp-SHC1GRB2SOS1 p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2PI3K p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG PLC gamma1/2 p-SHC1GRB2SOS p-SHC1GRB2SOS MALT1 trimer bound to Bcl10 and CARMA1 trimer GRB2SOS1 GADSp-Y113,Y128,Y145-SLP-76 p-10Y-NTALp-SHC1GRB2SOS GADSSLP76 PAK dimer DAGp-5Y-PKC-thetaCBM oligomer BCL10MALT1 p-SHC1GRB2SOS CBM oligomeroligo-K63-poly Ub-TRAF6 oligomer p-10Y-NTALp-SHC1GRB2SOS p-LYNp-FCERIIgE aggregate IP3 receptor homotetramer p-SHC1GRB2SOS GRB2SOS1 p-5Y-PKC-thetaDAG DAGp-5Y-PKC-thetap-S552,S645-CARMA1 oligomer p-SHC1GRB2SOS PLC gamma1/2 NFATCaNCaM GRB2SOS1 Immunoglobulin Kappa Light Chain IgE Heavy Chain RAC1-GTP PIP3, PIp-5Y-PKC-thetaDAG CaNCaMCa2+ p-5Y-LATp-SHC1GRB2SOS1 GADSp-Y113,Y128,Y145-SLP-76 p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2 GADSp-Y113,Y128,Y145-SLP-76 p-10Y-NTALp-SHC1GRB2SOS p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG NF-kB complex p21 RAS TAB2/3 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG Ig Heavy Chain V Region GADSp-Y113,Y128,Y145-SLP-76 Clustered pLYNp-FCERIIgEallerginSYK GADSp-Y113,Y128,Y145-SLP-76 Allerginp-LYNp-FCERIIgE aggregate PLC gamma1/2 PLC gamma1/2 Allerginp-LYNp-FCERIIgE aggregate DAGp-5Y-PKC-thetaCBM complex DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6 Ig Antibody Light Chain Immunoglobulin Kappa Light Chain p-SHC1GRB2SOS GRB2SOS1 PI3K-catalytic subunit GRB2SOS1 p-SHC1GRB2SOS PIP3, PITAB1TAB2/TAB3TAK1 TAB1TAB2/TAB3TAK1 PLC gamma1/2 GRB2SOS1 Ig Heavy Chain V Region Dephosphorylated NFATC1/2/3 RAC1-GTP VAV p-SHC1GRB2SOS PI3K-catalytic subunit p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG p-5Y-PKC-thetaDAG GADSSLP76 IgE p-5Y-PKC-thetaDAG p21 RAS p-5Y-LATp-SHC1GRB2SOS1GADSSLP76 GADSp-Y113,Y128,Y145-SLP-76 PKC-theta PI3K TAB2/3 p-PLCG CalcineurinCalmodulin p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-TEC kinasesPIP3 p-LYNp-FCERIIgE aggregate MALT1oligomerTRAF6 p-5Y-LATp-SHC1GRB2SOS1 FCERIG dimer IP3 receptorIP3 complex PPP3CA/BFe3+Zn2+ IgE Heavy Chain Active Calmodulin p-5Y-LATp-SHC1GRB2SOS1 GADSp-Y113,Y128,Y145-SLP-76 Active Calmodulin CaN catalytic alpha/betaZn++Fe3+CaMCa2+ p-SHC1GRB2SOS DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6TAK1TAB1TAB2/3 Bcl10 trimer bound to CARMA1 trimer IgE p-5Y-LATp-SHC1GRB2SOS1 p-5Y-PKC-thetaDAG GADSp-Y113,Y128,Y145-SLP-76 p-S177,S181-IKKBIKKANEMO Immunoglobulin Lambda Light Chain p-Y90-PKC-thetaDAG p-SHC1GRB2SOS Ig Lamda Light Chain V Region PPP3CA/B p-SHC1GRB2SOS p-5Y-LATp-SHC1GRB2SOS1 cytosolIkBGRB2SOS1 Allerginp-LYNp-FCERIIgE aggregate CARMA1 trimer Ig Lamda Light Chain V Region Ig Lamda Light Chain V Region p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVTEC kinasesPIP3 IGLV5-45Ig lambda chain V-IV region Kern Ig heavy chain V-I region SIE GDP ATPp-Y113,Y128,Y145-LCP2 Ig lambda chain V-II region NIG-84 GRAP2 SOS1 PPP3R1 p-S177,S181-IKKBIKKANEMOPIZn2+ IGLV2-33DAGs GRAP2 Ig lambda chain V-I region VOR Ig kappa chain V-II region RPMI 6410 Ig kappa chain V-II region TEW Ig heavy chain V-III region CAM VAV2 PIK3CB ITPR3 DAGs Ig heavy chain V-III region BUT Ig lambda chain V-IV region MOL Ig lambda chain V-V region DEL Ig lambda chain V-IV region Hil GRB2-1 DAGs TAB1 p-5Y-LAT-2 Ig kappa chain V-II region MIL p-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-I region EU ADPIg heavy chain V-II region HE K63polyUb TRAF6 IGLV1-36p-5Y-LAT-2 VAV1 GRAP2 IGLV5-45ATPIg lambda chain V-I region EPS IGLC6Ig kappa chain V-III region SIE PIIGKV1-5Ig heavy chain V-I region ND Ig heavy chain V-II region DAW Ig kappa chain V-I region HK101 ADPIg lambda chain V-I region NIG-64 Ig lambda chain V-I region NIG-64 IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region AU IGLV3-12PIIg kappa chain V-I region Scw Ig kappa chain V-I region EU Ig lambda chain V-II region NIG-84 PDK1PIP2,PIP3p-Y113,Y128,Y145-LCP2 p-Y1400,Y1412-MAP3K1Ig kappa chain V-II region Cum Ig kappa chain V region EV15 Ig lambda chain V-II region MGC DAGs GRB2-1 Ig heavy chain V-III region TEI Ig heavy chain V-III region DOB Ig heavy chain V-III region CAM Ig lambda chain V-I region EPS p-Y113,Y128,Y145-LCP2 ATPIGHVp-T325,T331,S362,S374-FOSIg heavy chain V-III region BUR Ig lambda chain V-III region LOI Ig kappa chain V-III region WOL Ig kappa chain V-I region WAT DAGp-5Y-PKC-thetap-S552,S645-CARMA1Ig heavy chain V-II region NEWM Ig kappa chain V-IV region JI IGLV2-23Ig heavy chain V-III region POM IGLV2-11CALM1 PLCG1Ig heavy chain V-III region BRO p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVADPIg heavy chain V-III region BRO ADPIg heavy chain V-III region POM PIIg heavy chain V-II region NEWM PRKCQ Ig heavy chain V-III region KOL Ig kappa chain V-II region FR p-S552,S645-CARD11Ig kappa chain V-II region MIL Ig lambda chain V-II region BOH PIK3CA p-S265-NFATC3 PLCG2 PIIGKCIg lambda chain V-VI region WLT ITPR2 Ig kappa chain V-III region IARC/BL41 Ig kappa chain V-I region Roy PPP3CA Ig kappa chain V-I region Ni p-Y113,Y128,Y145-LCP2 Ig kappa chain V-I region Ni MAP3K7 IkBIg heavy chain V-II region NEWM Ig heavy chain V-II region NEWM K63polyUb TRAF6 Ig kappa chain V-I region DEE Ig kappa chain V-I region BAN Ig kappa chain V-I region CAR Ig heavy chain V-I region ND Ig heavy chain V-III region WAS IGLV7-43Ig kappa chain V-II region GM607 GDP Ig lambda chain V-IV region Kern IGHEIg heavy chain V-III region GAL SOS1 ADPp-Y90,T219,T538,S676,S695-PRKCQ Ig lambda chain V-I region NEWM IGLV3-27Ig lambda chain V-I region WAH IGLC1ADPIg kappa chain V-III region NG9 IGKV4-1PIK3R1 ADPIg kappa chain V-III region HIC SOS1 Ig lambda chain V-II region NIG-58 Ig lambda chain V-II region WIN Ig lambda chain V-VI region NIG-48 Ig heavy chain V-I region HG3 ADPSOS1 Ig lambda chain V-II region BO NF-kB complexIGLV8-61Ig lambda chain V-II region NIG-58 PIK3CB Ca2+p-Y174-VAV1 ATPIg kappa chain V-I region HK101 PAK2IGLV3-12Ig heavy chain V-III region HIL PLCG1Ig kappa chain V-III region VG Ig kappa chain V-III region POM p-5Y-PKC-thetaDAGp-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-II region COR Ig lambda chain V-VI region WLT Ig kappa chain V-I region EU p-10Y-LAT2Ig kappa chain V-I region Ni DAGs GRB2-1 Ig kappa chain V-I region Lay Ig lambda chain V-I region NEWM Ig kappa chain V-III region SIE DAGsIGLV4-3IGLV4-3p-Y90,T219,T538,S676,S695-PRKCQ Ig lambda chain V-IV region Bau Ig kappa chain V-III region WOL Fe3+ p-Y396-LYNIg heavy chain V-II region WAH Ig kappa chain V-I region Lay SOS1 ADPp-Y239,Y240,Y317-SHC1-2PIIGLV3-25Ig kappa chain V-I region WEA Ig kappa chain V-I region Walker Ig kappa chain V-III region HIC ATPIg lambda chain V-II region NIG-84 FCER1G IGLV3-25SYK p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVTEC kinasesPIP3IGLV4-60p-Y174-VAV1 IGLV5-45IGLV1-40Ig lambda chain V-VI region EB4 DAGs p-Y172-VAV2 IGHV7-81Ig heavy chain V-II region ARH-77 p21 RASGTPIg lambda chain V-II region VIL IGHELAT-2p-Y90-PRKCQ Ig kappa chain V-I region Wes PPP3CBIGLV11-55PIK3R2 Ig heavy chain V-III region TIL Ig lambda chain V-I region VOR Ig kappa chain V-III region NG9 Ig kappa chain V-I region EU Ig heavy chain V-III region TUR ADPp-S177,S181-IKKBIKKApUb-NEMOAllerginp-LYNp-FCERIIgE aggregatePLCG2 Ig kappa chain V-II region Cum p-Y239,Y240,Y317-SHC1-2 DAGs IGLV4-60Ig lambda chain V-VI region AR PIPPiUBE2N Ig heavy chain V-II region WAH Ig kappa chain V-III region VH IGLV3-25Ig lambda chain V-II region MGC DAGs PLC gamma1/2IGLV2-23Ig lambda chain V region 4A p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTPPAK dimerIGLV4-69Ig kappa chain V-I region Daudi TAB3GRAP2 IGLVIGHV7-81AMPIg lambda chain V-II region WIN Ig heavy chain V-III region WEA Ig heavy chain V-III region TUR Ig kappa chain V-I region DEE Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-II region COR Ig heavy chain V-III region TIL Ig kappa chain V-III region HAH Ig heavy chain V-III region WEA SOS1 IGLV2-18IGKV4-1Ig kappa chain V-I region OU Ig lambda chain V-VI region EB4 Ig kappa chain V-II region MIL Ig kappa chain V-IV region STH VAV1 PRKQC closed conformationIg heavy chain V-III region WEA p-Y113,Y128,Y145-LCP2 K63polyUb TRAF6 NFKB1IGLV7-43Ig kappa chain V-I region WEA Ig kappa chain V-III region HIC GRAP2 IGKV1-5H2OIg kappa chain V-II region FR VAV3 PLCG2 Ig kappa chain V-IV region Len Ca2+ HRASCa2+ PPP3R1 GTP ATPIg heavy chain V-III region NIE PIIGLV5-37Ig kappa chain V-I region Rei p-5Y-LAT-2GRB2-1 Ig kappa chain V-I region Hau p-5Y-LAT-2 BCL10 IGLV2-33Ig kappa chain V-II region Cum Ig kappa chain V-III region VG ATPIGKVA18Ig heavy chain V-III region DOB Ig heavy chain V-II region HE Ig lambda chain V-I region WAH IGLV1-40Ig kappa chain V-III region IARC/BL41 Ca2+ Ig kappa chain V-IV region B17 TAB3IGLV7-46Ig lambda chain V-IV region Kern IGLV3-12Ig kappa chain V-III region VH Ig kappa chain V-III region POM Ig kappa chain V-I region Daudi Ig lambda chain V-I region VOR CARD11IGLV2-18Ig kappa chain V-III region CLL p-10Y-LAT2 GRB2-1 Ig lambda chain V region 4A RAC1 BCL10MALT1IGLV2-33Ig lambda chain V-I region NEW Ig kappa chain V region EV15 Ig kappa chain V-I region Ka DAGp-5Y-PKC-thetaCBM oligomerTRAF6Ig kappa chain V-I region Mev RasGRPsDAGCa2+SOS1 SOS1 IGLV4-69p-S63,S73-JUNIGKV1-5Clustered pLYNp-FCERIIgEallerginSYKIg heavy chain V-II region ARH-77 Ig kappa chain V-I region Kue CALM1 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-TEC kinasesIg lambda chain V-VI region WLT MALT1 Ig lambda chain V-II region WIN MALT1Ig kappa chain V-I region OU Ig heavy chain V-III region GAL Ig heavy chain V-III region BRO GRB2-1 RasGRPsPLCG1Ig lambda chain V-II region VIL Ig kappa chain V-I region AU MALT1 CHUK p-S243-NFATC2 ATPIIg heavy chain V-III region TRO Ig kappa chain V-I region Ka p-Y239,Y240,Y317-SHC1-2 GRB2-1 PLCG1Ig heavy chain V-III region JON ADPDAGs Ig kappa chain V-IV region JI p-Y90,T219,T538,S676,S695-PRKCQ Ig kappa chain V-III region NG9 Ig heavy chain V-II region COR Ig heavy chain V-III region LAY Ig heavy chain V-III region NIE Ig kappa chain V-I region Walker Ig heavy chain V-I region Mot Ig kappa chain V-III region Ti IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Ni Ig heavy chain V-I region ND Fe3+ ATPIg kappa chain V region EV15 PIP3 activates AKT signalingIg heavy chain V-III region CAM RAC1 Ig heavy chain V-I region HG3 Ig lambda chain V-II region BO ATPIGLC3PIK3R1 Ig heavy chain V-III region LAY Ig heavy chain V-II region OU CALM1 PLCG2 Ig lambda chain V-I region MEM Ig lambda chain V-III region LOI Ig heavy chain V-I region Mot K63polyUb TRAF6 Ig lambda chain V-VII region MOT Ig kappa chain V-III region IARC/BL41 Ig lambda chain V-I region BL2 Ig kappa chain V-I region OU GAB2 LYNIg heavy chain V-III region DOB Ig heavy chain V-III region BUT Ig kappa chain V-I region WEA Ig kappa chain V-III region VG p-S177,S181-IKBKB Ig kappa chain V-I region CAR GRAP2 IGLC2VAV2 CALM1 Ig lambda chain V-I region HA Phosphorylated NFATC1/2/3IGLV11-55Ig heavy chain V-I region WOL GTP p-6Y-SYK IGHEIg kappa chain V region EV15 NFATCaNCaMp-Y239,Y240,Y317-SHC1-2 p-Y113,Y128,Y145-LCP2 p-S63,S73-JUN Ig lambda chain V-I region NEW p-Y396-LYNp-4Y-PLCG1 PLCG2 IGLV5-37p-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-III region TRO Ig heavy chain V-II region WAH IGLV2-18Ig heavy chain V-III region JON IGKV1-5Ig lambda chain V-I region EPS Ig lambda chain V-II region NIG-58 Ig heavy chain V-III region TIL Ig lambda chain V-II region VIL PI3KTEC,BTK,ITK,ITPR3 Zn2+ Ig lambda chain V-III region LOI Ub-TRAF6 trimer bound to CBM complexIg kappa chain V-II region FR Ig kappa chain V-I region Wes IGKCKRASIg lambda chain V-I region WAH Ig heavy chain V-III region ZAP ADPIg heavy chain V-III region WAS p-4Y-PLCG2 DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6activated TAK1 complexRAC1 Ig heavy chain V-I region Mot IGLV3-16Ig kappa chain V-I region Daudi JUNATPMAPK8/9/10NFATCaNCaMIg heavy chain V-II region MCE Ig kappa chain V-I region AG Ig kappa chain V-III region CLL p-Y113,Y128,Y145-LCP2 IGADSSLP76p-5Y-LAT-2 Ig kappa chain V-III region HIC PDPK1 Ca2+IGKV4-1p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVIg lambda chain V-V region DEL Ig heavy chain V-III region GAL Ig kappa chain V-I region Roy K63polyUb-NEMO PiIg lambda chain V-II region NIG-84 Ig heavy chain V-III region CAM Ig kappa chain V-I region Ka Ig kappa chain V-III region GOL TRAF6Ig lambda chain V-I region EPS Ig kappa chain V-III region Ti Ig lambda chain V-I region NIG-64 Ig lambda chain V-I region BL2 Ig kappa chain V-III region GOL GDPADPIg heavy chain V-III region GA Ig lambda chain V-II region TOG IGLV3-25ATPATPp-S271,T275-MAP2K7ADPp-Y239,Y240,Y317-SHC1-2 VAV3 GRB2-1 PPP3CBIGLV3-12p-Y239,Y240,Y317-SHC1-2 MAP2K4PPP3CA DAGs NFKB1p-Y90,T219,T538,S676,S695-PRKCQ Ig heavy chain V-II region MCE IGLC3Ig lambda chain V-II region WIN Ig lambda chain V-I region MEM Ig heavy chain V-II region OU SOS1 p21 RASGDPIg heavy chain V-II region COR Ig kappa chain V-I region Bi Ig heavy chain V-III region LAY p-10Y-LAT2 Ig kappa chain V-I region Gal Ig kappa chain V-IV region STH Ig heavy chain V-III region ZAP PDPK1Ig heavy chain V-III region BUR ATPFe3+ Ig lambda chain V-I region WAH IGKVA18Ig heavy chain V-III region JON Ig heavy chain V-II region SESS IGLVIg heavy chain V-I region WOL Ig heavy chain V-III region POM Ig lambda chain V-VI region NIG-48 PLCG1IGLV7-46VAV1 Ig lambda chain V-VI region NIG-48 ADPVAV3 VAVRELA ATPIg kappa chain V-I region HK101 p-5Y-LAT-2 p-5Y-LAT-2 Ig heavy chain V-I region HG3 IGLV3-27Ig heavy chain V-III region TRO PIIg heavy chain V-III region GA CHUK p-Y239,Y240,Y317-SHC1-2 Ig lambda chain V-I region MEM p-5Y-LAT-2 Ig heavy chain V-III region GA SYKIg heavy chain V-I region SIE p-10Y-NTALp-SHC1GRB2SOSVAV1 Ig lambda chain V-VII region MOT IGLV11-55GRB2-1 p-Y173-VAV3 Ig lambda chain V-IV region Hil Ig heavy chain V-III region WAS Ig kappa chain V-IV region B17 Ig lambda chain V-VI region AR p-T325,T331,S362,S374-FOS IGKV4-1Ig kappa chain V-I region Mev IGLV1-40Ig kappa chain V-II region RPMI 6410 FCERIIgEallergin aggregateIgH heavy chain V-III region VH26 precursor Ig lambda chain V-II region BUR Ig kappa chain V-I region EU IGLV7-46IGLV3-16Ig kappa chain V-I region HK101 VAV3 Ig heavy chain V-III region POM Ig lambda chain V-II region TRO RAF/MAP kinase cascadeIGLC2NRAS IGLV7-46ATPPLCG1Ig kappa chain V-I region Mev Ca2+ TAB1TAB2/TAB3TAK1PIIg lambda chain V-I region MEM Ig lambda chain V-II region BUR p-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-III region DOB ADPIg kappa chain V-I region Daudi SOS1 p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2PI3KLCP2 Ig kappa chain V-I region Kue UBE2V1 p-Y113,Y128,Y145-LCP2 IKBKG H2OIg kappa chain V-I region WAT Ig kappa chain V-II region GM607 BCL10IGLV4-69Ca2+ K63polyUbIg kappa chain V-III region WOL GRAP2 Ig kappa chain V-I region Hau IGLC6TAB2 Ig kappa chain V-I region Scw Ig heavy chain V-III region ZAP PIIg kappa chain V-I region AU Ig heavy chain V-III region KOL Ig lambda chain V-III region SH VAV3 Ig kappa chain V-I region OU IGHVGRB2-1 PIIg kappa chain V-II region GM607 DAGs p-Y90,T219,T538,S676,S695-PRKCQ Ig lambda chain V-I region NIG-64 p-2S-cJUNp-2S,2T-cFOSp-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-III region Ti Ig lambda chain V region 4A SOS1 IGHV7-81ADPADPp-S257-NFATC1 IGLC1Ig kappa chain V-I region Bi IKBKB IGHEGRB2-1 PLCG1Ig lambda chain V-IV region X Ig lambda chain V-II region TRO Ig lambda chain V-II region TRO PIK3R2 p-Y173-VAV3 Ig heavy chain V-I region HG3 GRAP2 Ig kappa chain V-I region Rei IGLV5-45ADPVAV2 TAB1 SHC1-2MAP3K7 BCL10 Ig kappa chain V-III region VG Ig lambda chain V-II region NIG-58 Ig heavy chain V-III region NIE Ig lambda chain V-I region BL2 SOS1 Ig lambda chain V-I region HA Ig kappa chain V-I region Gal ATPp-Y239,Y240,Y317-SHC1-2 GTPp-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-III region HIL ATPIg heavy chain V-II region SESS ADPIg heavy chain V-III region GAL Ubc13UBE2V1IGLC3IGLV1-36Ig heavy chain V-III region HIL Ig kappa chain V-III region POM p-Y90,T219,T538,S676,S695-PRKCQ Ig heavy chain V-III region TUR PAK dimerp-S265-NFATC3 Ig kappa chain V-III region B6 Ig heavy chain V-I region EU IP3 receptorIP3 complexVAV2 Ig lambda chain V-IV region Bau Ig kappa chain V-I region Bi FCER1A Ig kappa chain V-IV region JI Ig kappa chain V-III region POM IGLV1-36Ig kappa chain V-II region TEW Ig kappa chain V-III region B6 Ig kappa chain V-II region TEW IGLV2-33Ig kappa chain V-II region FR Ig heavy chain V-I region EU p-Y174-VAV1 PAK1 Ig kappa chain V-III region WOL VAV2 CHUK IGLV8-61Active CalmodulinCalcineurinCalmodulin DAGp-5Y-PKC-thetap-S552,S645-CARMA1 oligomerIg lambda chain V-I region BL2 DAGp-5Y-PKC-thetaCBM complexIg lambda chain V-II region BO LCP2 Ig heavy chain V-III region BUT PDPK1 p-S243-NFATC2 p-MAPK8/9/10Ig heavy chain V-III region JON MAP3K1Ig kappa chain V-III region VH p-Y90,T219,T538,S676,S695-PRKCQ PKC-theta IGLC3Ig kappa chain V-I region Rei SOS1 Ig kappa chain V-I region Mev Ig lambda chain V-IV region Kern Ig heavy chain V-III region BUR DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6TAK1TAB1TAB2/3NFKBIA IGLV3-22ATPIg lambda chain V-II region TOG TRAF6 GRAP2 MALT1 Ig kappa chain V-I region Gal Ig lambda chain V-IV region Bau Ig lambda chain V-I region NEWM IGLV3-16ITPR1 PPP3CA DAGs Ig heavy chain V-II region OU Ca2+UBE2V1 Ig lambda chain V-I region NEWM Ig lambda chain V-II region TOG Calcineurin p-Y173-VAV3 Ig kappa chain V-I region DEE Ig heavy chain V-II region SESS IGLV1-44p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2p-10Y-LAT2 Ig heavy chain V-III region BUR Ig lambda chain V-VI region NIG-48 Ig kappa chain V-I region Scw IGLC2Ig heavy chain V-II region HE GRB2-1 ITPR2 GAB2p-S552,S645-CARD11IGKVA18Ig heavy chain V-I region WOL Ig lambda chain V-II region NEI ATPp-Y90,T219,T538,S676,S695-PRKCQ Ig kappa chain V-I region Wes DAGsIg lambda chain V-IV region Hil PIIg lambda chain V-I region NEW NFKB1MS4A2 SOS1 p-Y113,Y128,Y145-LCP2 ADPIg kappa chain V-I region Gal p-Y90,T219,T538,S676,S695-PRKCQ IGLV10-54Ubc13UBE2V1IGLV2-11Ig kappa chain V-IV region Len Ig kappa chain V-I region Kue PLCG2 Ig kappa chain V-I region Wes Ig lambda chain V-IV region MOL IGLV10-54Ig lambda chain V-IV region Hil p-5Y-LAT-2 RELA IGLV5-37Ig heavy chain V-III region HIL p-5Y-LATp-SHC1GRB2SOS1GADSSLP76GRB2-1 Ig lambda chain V-IV region X Ig kappa chain V-III region NG9 Ig kappa chain V-II region TEW Ig kappa chain V-I region Ka Ig heavy chain V-II region DAW Ig lambda chain V region 4A PISOS1 Ig kappa chain V-I region BAN ADPIGLVIGLV7-43p-Y90,T219,T538,S676,S695-PRKCQ IGKCIGLV1-44Ig heavy chain V-III region KOL Ig kappa chain V-IV region STH Ig lambda chain V-VI region AR PIIGHVZn2+ Ig heavy chain V-II region MCE Ig kappa chain V-II region RPMI 6410 IP3 receptor homotetramerIg heavy chain V-III region TIL p-5Y-LAT-2 p-5Y-LATp-SHC1GRB2SOS1Ig lambda chain V-VI region SUT Ig heavy chain V-II region HE FOSIg lambda chain V-I region HA Ig kappa chain V-I region AG DAGp-5Y-PKC-thetaCBM oligomerIg kappa chain V-I region Lay Ig kappa chain V-I region CAR ATPp-10Y-LAT2 Ig lambda chain V-V region DEL Ig lambda chain V-VI region SUT Ig lambda chain V-I region HA Ig heavy chain V-III region TUR PPP3R1 PIP3, PIPLCG2 IGLV3-27GRB2-1 Ig heavy chain V-I region WOL IGLV3-22Ig heavy chain V-II region ARH-77 Ig lambda chain V-VI region SUT p-Y172-VAV2 p-S32,S36-NFKBIAIGLV2-11NRAS IGHV7-81p-5Y-LATp-SHC1GRB2SOS1GADSSLP76PLCGIg kappa chain V-IV region Len Ig heavy chain V-III region KOL p-S257,T261-MAP2K4Ig kappa chain V-I region WEA Ig kappa chain V-I region CAR p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-BTK/p-2Y-ITKPIP3GRB2-1 TAB1 Ig lambda chain V-III region SH Ig lambda chain V-II region BOH KRASGTP IGLV10-54p-10Y-NTALp-SHC1GRB2SOSGAB2p-Y239,Y240,Y317-SHC1-2 Ig lambda chain V-II region VIL ATPIGLV4-69Ig kappa chain V-I region BAN ATPADPGRB2-1 Ig heavy chain V-I region SIE p-2Y-PAKPhospho-ERK dimerIg kappa chain V-III region GOL PIIg kappa chain V-I region WAT IGLV2-23IGLV4-60Ig lambda chain V-VI region EB4 Ig lambda chain V-III region SH Ig lambda chain V-VI region EB4 GRAP2 Ig heavy chain V-I region Mot Clustered pLYNp-FCERIIgEallerginp-6Y-SYKIGLV4-60DAGp-5Y-PKC-thetaCBM oligomerTRAF6 oligomerCALM1p-5Y-LAT-2 Ig kappa chain V-I region Lay IGLV8-61TAB2 IGLC7Ig lambda chain V-II region BOH PLCG1SOS1 p-SHC1GRB2SOSIg heavy chain V-I region EU Ig kappa chain V-III region B6 IKKAIKKBNEMOPPP3CBp-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTPIGKCIg heavy chain V-III region TEI Ig lambda chain V-VI region SUT Ig kappa chain V-IV region Len p-Y239,Y240,Y317-SHC1-2 Ig lambda chain V-V region DEL Ig lambda chain V-II region MGC PPP3CA VAV1 Ig kappa chain V-IV region JI ADPIgH heavy chain V-III region VH26 precursor Ig lambda chain V-I region NEW Ig kappa chain V-III region GOL GRAP2 IGLV7-43Ig kappa chain V-I region Rei Ig kappa chain V-III region CLL ITPR1 NF-kB complexIg kappa chain V-III region CLL IGLV11-55p-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-II region WAH Ig lambda chain V-I region VOR ATPMAP2K7Ig kappa chain V-I region Walker Ig lambda chain V-VI region AR Ig kappa chain V-I region Hau PLCG2 LAT2GRB2SOS1IGKVA18HRASIg kappa chain V-I region Roy Ig kappa chain V-I region Kue GRB2-1 Ig kappa chain V-IV region B17 IGLV10-54IGLV1-40RAC1-GDPIg kappa chain V-III region B6 p-S552-CARD11Ig lambda chain V-II region NEI IGLC7Ig heavy chain V-III region GA Ig heavy chain V-I region SIE Ig heavy chain V-III region LAY DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6IGLV4-3IGLC6Ig kappa chain V-I region BAN GRAP2 GDPIg kappa chain V-I region AG IGLV8-61IGLV1-36IGHVp-Y90-PKC-thetaDAGIg heavy chain V-III region WEA Ig lambda chain V-IV region X IGLV3-16Ig lambda chain V-II region TOG Ig lambda chain V-II region BUR p-MAP2K4/p-MAP2K7PIK3CA Zn2+ Ig kappa chain V-IV region B17 Ig kappa chain V-III region SIE p-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-III region BUT Ig kappa chain V-II region MIL Ig lambda chain V-VII region MOT PPP3CBIg lambda chain V-II region MGC Ig kappa chain V-III region Ti TAB3IGLC1ADPRELA IGLVGRB2-1 ATPIg kappa chain V-III region HAH p-Y396-LYNIg kappa chain V-I region Scw Ig lambda chain V-IV region MOL p-5Y-LAT-2 Ig lambda chain V-II region BOH IGLV5-37PIIg heavy chain V-I region ND GTPIg heavy chain V-III region TEI Ig kappa chain V-I region WAT IGLV3-22p-Y452,Y476,Y584-GAB2 Ig lambda chain V-II region TRO SOS1 K63polyUbFe3+ p-Y452,Y476,Y584-GAB2 Ig kappa chain V-I region Hau p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-TEC kinasesPIP3Ig heavy chain V-III region TEI p-5Y-LAT-2 LCP2 Ig kappa chain V-II region Cum TAB2 Ig lambda chain V-III region LOI IGLV2-23PIIg lambda chain V-II region NEI Ig heavy chain V-II region ARH-77 Ig heavy chain V-III region BRO Ig kappa chain V-III region HAH Ig lambda chain V-II region NEI Ig kappa chain V-III region IARC/BL41 PIp-SYK/p-BTKIg lambda chain V-VI region WLT Ig kappa chain V-I region Bi Ig lambda chain V-II region BO Ig kappa chain V-IV region STH Ig lambda chain V-IV region MOL IKBKG Ig heavy chain V-II region DAW ATPPPP3R1 SYK/FYNIg kappa chain V-I region Roy Ig kappa chain V-I region AU Ig heavy chain V-III region WAS SOS1 IGLC6IGLC7IGLV4-3UBE2N Ig kappa chain V-III region SIE MAP3K7 FCERIIgEIGLV3-22p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCGp-Y396-LYNIGLV3-27Ig heavy chain V-III region NIE IGLC7Ig kappa chain V-I region AG IGLC1p-MAPK8/9/10Ig heavy chain V-III region ZAP Ig lambda chain V-IV region X p-S257-NFATC1 Ig kappa chain V-I region Walker IGLV1-44Ig lambda chain V-III region SH IGLC2DAGs Ig lambda chain V-VII region MOT PLCG1Ig kappa chain V-III region HAH Ig heavy chain V-II region DAW Ig lambda chain V-IV region Bau Ig kappa chain V-II region GM607 IGLV2-18Ig kappa chain V-III region VH p-S177,S181-IKBKB ADPPLCG2 Ig heavy chain V-III region TRO p-BCL10 Allerginp-Y172-VAV2 IGLV2-11IGLV1-44Ig kappa chain V-I region DEE Ig heavy chain V-II region MCE Ig heavy chain V-II region OU Ig heavy chain V-II region SESS Ig lambda chain V-II region BUR PI353535656591, 966535653598353535442935


Description

Mast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory and immediate allergic reactions. Activation through FCERI-bound antigen-specific IgE causes release of potent inflammatory mediators, such as histamine, proteases, chemotactic factors, cytokines and metabolites of arachidonic acid that act on the vasculature, smooth muscle, connective tissue, mucous glands and inflammatory cells (Borish & Joseph 1992, Amin 2012, Metcalfe et al. 1993). FCERI is a multimeric cell-surface receptor that binds the Fc fragment of IgE with high affinity. On mast cells and basophils FCERI exists as a tetrameric complex consisting of one alpha-chain, one beta-chain, and two disulfide-bonded gamma-chains, and on dendritic cells, Langerhans cells, macrophages, and eosinophils it exists as a trimeric complex with one alpha-chain and two disulfide-bonded gamma-chains (Wu 2011, Kraft & Kinet 2007). FCERI signaling in mast cells includes a network of signaling molecules and adaptor proteins. These molecules coordinate ultimately leading to effects on degranulation, eicosanoid production, and cytokine and chemokine production and cell migration and adhesion, growth and survival.
The first step in FCERI signaling is the phosphorylation of the tyrosine residues in the ITAM of both the beta and the gamma subunits of the FCERI by LYN, which is bound to the FCERI beta-chain. The phosphorylated ITAM then recruits the protein tyrosine kinase SYK (spleen tyrosine kinase) which then phosphorylates the adaptor protein LAT. Phosphorylated LAT (linker for activation of T cells) acts as a scaffolding protein and recruits other cytosolic adaptor molecules GRB2 (growth-factor-receptor-bound protein 2), GADS (GRB2-related adaptor protein), SHC (SRC homology 2 (SH2)-domain-containing transforming protein C) and SLP76 (SH2-domain-containing leukocyte protein of 76 kDa), as well as the exchange factors and adaptor molecules VAV and SOS (son of sevenless homologue), and the signalling enzyme phospholipase C gamma1 (PLC-gamma1). Tyrosoine phosphorylation of enzymes and adaptors, including VAV, SHC GRB2 and SOS stimulate small GTPases such as RAC, RAS and RAF. These pathways lead to activation of the ERK, JNK and p38 MAP kinases, histamine release and cytokine production. FCERI activation also triggers the phosphorylation of PLC-gamma which upon membrane localisation hydrolyse PIP2 to form IP3 and 1,2-diacylglycerol (DAG) - second messengers that release Ca2+ from internal stores and activate PKC, respectively. Degranulation or histamine release follows the activation of PLC-gamma and protein kinase C (PKC) and the increased mobilization of calcium (Ca2+). Receptor aggregation also results in the phosphorylation of adaptor protein NTAL/LAT2 which then recruits GAB2. PI3K associates with phosphorylated GAB2 and catalyses the formation of PIP3 in the membrane, which attracts many PH domain proteins like BTK, PLC-gamma, AKT and PDK. PI3K mediated activation of AKT then regulate the mast cell proliferation, development and survival (Gu et al. 2001). Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=2454202

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Roskoski R.; ''RAF protein-serine/threonine kinases: structure and regulation.''; PubMed Europe PMC Scholia
  2. Turjanski AG, Vaqué JP, Gutkind JS.; ''MAP kinases and the control of nuclear events.''; PubMed Europe PMC Scholia
  3. Yablonski D, Kadlecek T, Weiss A.; ''Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.''; PubMed Europe PMC Scholia
  4. Shen X, Li H, Ou Y, Tao W, Dong A, Kong J, Ji C, Yu S.; ''The secondary structure of calcineurin regulatory region and conformational change induced by calcium/calmodulin binding.''; PubMed Europe PMC Scholia
  5. Reeve JL, Zou W, Liu Y, Maltzman JS, Ross FP, Teitelbaum SL.; ''SLP-76 couples Syk to the osteoclast cytoskeleton.''; PubMed Europe PMC Scholia
  6. Bubeck Wardenburg J, Fu C, Jackman JK, Flotow H, Wilkinson SE, Williams DH, Johnson R, Kong G, Chan AC, Findell PR.; ''Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function.''; PubMed Europe PMC Scholia
  7. Spencer E, Jiang J, Chen ZJ.; ''Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCP.''; PubMed Europe PMC Scholia
  8. Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE.; ''Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling.''; PubMed Europe PMC Scholia
  9. Hendricks-Taylor LR, Motto DG, Zhang J, Siraganian RP, Koretzky GA.; ''SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells.''; PubMed Europe PMC Scholia
  10. Bonizzi G, Karin M.; ''The two NF-kappaB activation pathways and their role in innate and adaptive immunity.''; PubMed Europe PMC Scholia
  11. Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF.; ''NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways.''; PubMed Europe PMC Scholia
  12. Liu SK, Fang N, Koretzky GA, McGlade CJ.; ''The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors.''; PubMed Europe PMC Scholia
  13. Plotnikov A, Zehorai E, Procaccia S, Seger R.; ''The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.''; PubMed Europe PMC Scholia
  14. Parrini MC, Lei M, Harrison SC, Mayer BJ.; ''Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1.''; PubMed Europe PMC Scholia
  15. Young RM, Holowka D, Baird B.; ''A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation.''; PubMed Europe PMC Scholia
  16. Roberts PJ, Der CJ.; ''Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer.''; PubMed Europe PMC Scholia
  17. Tkaczyk C, Horejsi V, Iwaki S, Draber P, Samelson LE, Satterthwaite AB, Nahm DH, Metcalfe DD, Gilfillan AM.; ''NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation.''; PubMed Europe PMC Scholia
  18. Manetz TS, Gonzalez-Espinosa C, Arudchandran R, Xirasagar S, Tybulewicz V, Rivera J.; ''Vav1 regulates phospholipase cgamma activation and calcium responses in mast cells.''; PubMed Europe PMC Scholia
  19. Tybulewicz VL, Ardouin L, Prisco A, Reynolds LF.; ''Vav1: a key signal transducer downstream of the TCR.''; PubMed Europe PMC Scholia
  20. Rusnak F, Mertz P.; ''Calcineurin: form and function.''; PubMed Europe PMC Scholia
  21. Blank U, Rivera J.; ''The ins and outs of IgE-dependent mast-cell exocytosis.''; PubMed Europe PMC Scholia
  22. Lu W, Mayer BJ.; ''Mechanism of activation of Pak1 kinase by membrane localization.''; PubMed Europe PMC Scholia
  23. Latres E, Chiaur DS, Pagano M.; ''The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin.''; PubMed Europe PMC Scholia
  24. Krappmann D, Hatada EN, Tegethoff S, Li J, Klippel A, Giese K, Baeuerle PA, Scheidereit C.; ''The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not IKAP as a regular component.''; PubMed Europe PMC Scholia
  25. Häcker H, Karin M.; ''Regulation and function of IKK and IKK-related kinases.''; PubMed Europe PMC Scholia
  26. Cuenda A, Dorow DS.; ''Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase kinase (MKK) kinase-1.''; PubMed Europe PMC Scholia
  27. Matsuda M, Paterson HF, Rodriguez R, Fensome AC, Ellis MV, Swann K, Katan M.; ''Real time fluorescence imaging of PLC gamma translocation and its interaction with the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
  28. Loh C, Shaw KT, Carew J, Viola JP, Luo C, Perrino BA, Rao A.; ''Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity.''; PubMed Europe PMC Scholia
  29. DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M.; ''A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB.''; PubMed Europe PMC Scholia
  30. Roskoski R.; ''ERK1/2 MAP kinases: structure, function, and regulation.''; PubMed Europe PMC Scholia
  31. Peng Q, Malhotra S, Torchia JA, Kerr WG, Coggeshall KM, Humphrey MB.; ''TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1.''; PubMed Europe PMC Scholia
  32. Gross BS, Lee JR, Clements JL, Turner M, Tybulewicz VL, Findell PR, Koretzky GA, Watson SP.; ''Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets.''; PubMed Europe PMC Scholia
  33. Wellbrock C, Karasarides M, Marais R.; ''The RAF proteins take centre stage.''; PubMed Europe PMC Scholia
  34. Nishida K, Yamasaki S, Hasegawa A, Iwamatsu A, Koseki H, Hirano T.; ''Gab2, via PI-3K, regulates ARF1 in FcεRI-mediated granule translocation and mast cell degranulation.''; PubMed Europe PMC Scholia
  35. Dong W, Liu Y, Peng J, Chen L, Zou T, Xiao H, Liu Z, Li W, Bu Y, Qi Y.; ''The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4.''; PubMed Europe PMC Scholia
  36. Brown MD, Sacks DB.; ''Protein scaffolds in MAP kinase signalling.''; PubMed Europe PMC Scholia
  37. Davis RJ.; ''MAPKs: new JNK expands the group.''; PubMed Europe PMC Scholia
  38. Song JS, Haleem-Smith H, Arudchandran R, Gomez J, Scott PM, Mill JF, Tan TH, Rivera J.; ''Tyrosine phosphorylation of Vav stimulates IL-6 production in mast cells by a Rac/c-Jun N-terminal kinase-dependent pathway.''; PubMed Europe PMC Scholia
  39. Altman A, Villalba M.; ''Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death.''; PubMed Europe PMC Scholia
  40. Kroll M, Conconi M, Desterro MJ, Marin A, Thomas D, Friguet B, Hay RT, Virelizier JL, Arenzana-Seisdedos F, Rodriguez MS.; ''The carboxy-terminus of I kappaB alpha determines susceptibility to degradation by the catalytic core of the proteasome.''; PubMed Europe PMC Scholia
  41. Alvarez-Errico D, Lessmann E, Rivera J.; ''Adapters in the organization of mast cell signaling.''; PubMed Europe PMC Scholia
  42. Dennler S, Prunier C, Ferrand N, Gauthier JM, Atfi A.; ''c-Jun inhibits transforming growth factor beta-mediated transcription by repressing Smad3 transcriptional activity.''; PubMed Europe PMC Scholia
  43. Cseh B, Doma E, Baccarini M.; ''"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.''; PubMed Europe PMC Scholia
  44. Qiu L, Dhe-Paganon S.; ''Oligomeric structure of the MALT1 tandem Ig-like domains.''; PubMed Europe PMC Scholia
  45. Alkalay I, Yaron A, Hatzubai A, Orian A, Ciechanover A, Ben-Neriah Y.; ''Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathway.''; PubMed Europe PMC Scholia
  46. Jabril-Cuenod B, Zhang C, Scharenberg AM, Paolini R, Numerof R, Beaven MA, Kinet JP.; ''Syk-dependent phosphorylation of Shc. A potential link between FcepsilonRI and the Ras/mitogen-activated protein kinase signaling pathway through SOS and Grb2.''; PubMed Europe PMC Scholia
  47. Iwaki S, Spicka J, Tkaczyk C, Jensen BM, Furumoto Y, Charles N, Kovarova M, Rivera J, Horejsi V, Metcalfe DD, Gilfillan AM.; ''Kit- and Fc epsilonRI-induced differential phosphorylation of the transmembrane adaptor molecule NTAL/LAB/LAT2 allows flexibility in its scaffolding function in mast cells.''; PubMed Europe PMC Scholia
  48. Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D.; ''Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.''; PubMed Europe PMC Scholia
  49. Sato S, Sanjo H, Takeda K, Ninomiya-Tsuji J, Yamamoto M, Kawai T, Matsumoto K, Takeuchi O, Akira S.; ''Essential function for the kinase TAK1 in innate and adaptive immune responses.''; PubMed Europe PMC Scholia
  50. Melowic HR, Stahelin RV, Blatner NR, Tian W, Hayashi K, Altman A, Cho W.; ''Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Ctheta.''; PubMed Europe PMC Scholia
  51. Okazaki K, Sagata N.; ''The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.''; PubMed Europe PMC Scholia
  52. Lennartsson J, Blume-Jensen P, Hermanson M, Pontén E, Carlberg M, Rönnstrand L.; ''Phosphorylation of Shc by Src family kinases is necessary for stem cell factor receptor/c-kit mediated activation of the Ras/MAP kinase pathway and c-fos induction.''; PubMed Europe PMC Scholia
  53. Wang X, Chuang HC, Li JP, Tan TH.; ''Regulation of PKC-θ function by phosphorylation in T cell receptor signaling.''; PubMed Europe PMC Scholia
  54. Chong C, Tan L, Lim L, Manser E.; ''The mechanism of PAK activation. Autophosphorylation events in both regulatory and kinase domains control activity.''; PubMed Europe PMC Scholia
  55. Siraganian RP.; ''Mast cell signal transduction from the high-affinity IgE receptor.''; PubMed Europe PMC Scholia
  56. Hayden MS, Ghosh S.; ''Signaling to NF-kappaB.''; PubMed Europe PMC Scholia
  57. Oeckinghaus A, Wegener E, Welteke V, Ferch U, Arslan SC, Ruland J, Scheidereit C, Krappmann D.; ''Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation.''; PubMed Europe PMC Scholia
  58. Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A.; ''Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells.''; PubMed Europe PMC Scholia
  59. Nore BF, Mattsson PT, Antonsson P, Bäckesjö CM, Westlund A, Lennartsson J, Hansson H, Löw P, Rönnstrand L, Smith CI.; ''Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases.''; PubMed Europe PMC Scholia
  60. Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG.; ''Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation.''; PubMed Europe PMC Scholia
  61. Sun L, Deng L, Ea CK, Xia ZP, Chen ZJ.; ''The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes.''; PubMed Europe PMC Scholia
  62. Deacon K, Blank JL.; ''Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.''; PubMed Europe PMC Scholia
  63. Fukumoto T, Kubota Y, Kitanaka A, Yamaoka G, Ohara-Waki F, Imataki O, Ohnishi H, Ishida T, Tanaka T.; ''Gab1 transduces PI3K-mediated erythropoietin signals to the Erk pathway and regulates erythropoietin-dependent proliferation and survival of erythroid cells.''; PubMed Europe PMC Scholia
  64. Zhao ZS, Manser E.; ''PAK and other Rho-associated kinases--effectors with surprisingly diverse mechanisms of regulation.''; PubMed Europe PMC Scholia
  65. Vanhaesebroeck B, Alessi DR.; ''The PI3K-PDK1 connection: more than just a road to PKB.''; PubMed Europe PMC Scholia
  66. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
  67. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ.; ''TAK1 is a ubiquitin-dependent kinase of MKK and IKK.''; PubMed Europe PMC Scholia
  68. Wu J, Motto DG, Koretzky GA, Weiss A.; ''Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation.''; PubMed Europe PMC Scholia
  69. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMed Europe PMC Scholia
  70. Kim YJ, Sekiya F, Poulin B, Bae YS, Rhee SG.; ''Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2.''; PubMed Europe PMC Scholia
  71. Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, Witte ON.; ''Regulation of Btk function by a major autophosphorylation site within the SH3 domain.''; PubMed Europe PMC Scholia
  72. Liu Y, Graham C, Li A, Fisher RJ, Shaw S.; ''Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction.''; PubMed Europe PMC Scholia
  73. Rhee SG.; ''Regulation of phosphoinositide-specific phospholipase C.''; PubMed Europe PMC Scholia
  74. Holowka D, Sil D, Torigoe C, Baird B.; ''Insights into immunoglobulin E receptor signaling from structurally defined ligands.''; PubMed Europe PMC Scholia
  75. Carter RS, Geyer BC, Xie M, Acevedo-Suárez CA, Ballard DW.; ''Persistent activation of NF-kappa B by the tax transforming protein involves chronic phosphorylation of IkappaB kinase subunits IKKbeta and IKKgamma.''; PubMed Europe PMC Scholia
  76. Garman SC, Wurzburg BA, Tarchevskaya SS, Kinet JP, Jardetzky TS.; ''Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha.''; PubMed Europe PMC Scholia
  77. Shiue L, Green J, Green OM, Karas JL, Morgenstern JP, Ram MK, Taylor MK, Zoller MJ, Zydowsky LD, Bolen JB.; ''Interaction of p72syk with the gamma and beta subunits of the high-affinity receptor for immunoglobulin E, Fc epsilon RI.''; PubMed Europe PMC Scholia
  78. Donella-Deana A, Cesaro L, Ruzzene M, Brunati AM, Marin O, Pinna LA.; ''Spontaneous autophosphorylation of Lyn tyrosine kinase at both its activation segment and C-terminal tail confers altered substrate specificity.''; PubMed Europe PMC Scholia
  79. Kishimoto K, Matsumoto K, Ninomiya-Tsuji J.; ''TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop.''; PubMed Europe PMC Scholia
  80. Gilmore TD.; ''Introduction to NF-kappaB: players, pathways, perspectives.''; PubMed Europe PMC Scholia
  81. Jiang Y, Cheng H.; ''Evidence of LAT as a dual substrate for Lck and Syk in T lymphocytes.''; PubMed Europe PMC Scholia
  82. Kanayama A, Seth RB, Sun L, Ea CK, Hong M, Shaito A, Chiu YH, Deng L, Chen ZJ.; ''TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains.''; PubMed Europe PMC Scholia
  83. Thuille N, Heit I, Fresser F, Krumböck N, Bauer B, Leuthaeusser S, Dammeier S, Graham C, Copeland TD, Shaw S, Baier G.; ''Critical role of novel Thr-219 autophosphorylation for the cellular function of PKCtheta in T lymphocytes.''; PubMed Europe PMC Scholia
  84. Bos JL, Rehmann H, Wittinghofer A.; ''GEFs and GAPs: critical elements in the control of small G proteins.''; PubMed Europe PMC Scholia
  85. Jevremovic D, Billadeau DD, Schoon RA, Dick CJ, Irvin BJ, Zhang W, Samelson LE, Abraham RT, Leibson PJ.; ''Cutting edge: a role for the adaptor protein LAT in human NK cell-mediated cytotoxicity.''; PubMed Europe PMC Scholia
  86. Hogan PG, Chen L, Nardone J, Rao A.; ''Transcriptional regulation by calcium, calcineurin, and NFAT.''; PubMed Europe PMC Scholia
  87. Dinh M, Grunberger D, Ho H, Tsing SY, Shaw D, Lee S, Barnett J, Hill RJ, Swinney DC, Bradshaw JM.; ''Activation mechanism and steady state kinetics of Bruton's tyrosine kinase.''; PubMed Europe PMC Scholia
  88. Baldi L, Brown K, Franzoso G, Siebenlist U.; ''Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alpha.''; PubMed Europe PMC Scholia
  89. Roskoski R.; ''MEK1/2 dual-specificity protein kinases: structure and regulation.''; PubMed Europe PMC Scholia
  90. Carter RS, Pennington KN, Ungurait BJ, Arrate P, Ballard DW.; ''Signal-induced ubiquitination of I kappaB Kinase-beta.''; PubMed Europe PMC Scholia
  91. Mizukami Y, Yoshioka K, Morimoto S, Yoshida Ki.; ''A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion.''; PubMed Europe PMC Scholia
  92. Parrini MC, Camonis J, Matsuda M, de Gunzburg J.; ''Dissecting activation of the PAK1 kinase at protrusions in living cells.''; PubMed Europe PMC Scholia
  93. Yu M, Lowell CA, Neel BG, Gu H.; ''Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit signals from FcepsilonRI.''; PubMed Europe PMC Scholia
  94. Aghazadeh B, Lowry WE, Huang XY, Rosen MK.; ''Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation.''; PubMed Europe PMC Scholia
  95. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA.; ''Mutations of the BRAF gene in human cancer.''; PubMed Europe PMC Scholia
  96. Rothwarf DM, Zandi E, Natoli G, Karin M.; ''IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex.''; PubMed Europe PMC Scholia
  97. Vonakis BM, Chen H, Haleem-Smith H, Metzger H.; ''The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE.''; PubMed Europe PMC Scholia
  98. Park S, Uesugi M, Verdine GL.; ''A second calcineurin binding site on the NFAT regulatory domain.''; PubMed Europe PMC Scholia
  99. Tanner MJ, Hanel W, Gaffen SL, Lin X.; ''CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation.''; PubMed Europe PMC Scholia
  100. Harmer SL, DeFranco AL.; ''Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes.''; PubMed Europe PMC Scholia
  101. Murphy LO, Smith S, Chen RH, Fingar DC, Blenis J.; ''Molecular interpretation of ERK signal duration by immediate early gene products.''; PubMed Europe PMC Scholia
  102. Shambharkar PB, Blonska M, Pappu BP, Li H, You Y, Sakurai H, Darnay BG, Hara H, Penninger J, Lin X.; ''Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways.''; PubMed Europe PMC Scholia
  103. Raivich G.; ''c-Jun expression, activation and function in neural cell death, inflammation and repair.''; PubMed Europe PMC Scholia
  104. Adhikari A, Xu M, Chen ZJ.; ''Ubiquitin-mediated activation of TAK1 and IKK.''; PubMed Europe PMC Scholia
  105. Cantwell-Dorris ER, O'Leary JJ, Sheils OM.; ''BRAFV600E: implications for carcinogenesis and molecular therapy.''; PubMed Europe PMC Scholia
  106. Teramoto H, Salem P, Robbins KC, Bustelo XR, Gutkind JS.; ''Tyrosine phosphorylation of the vav proto-oncogene product links FcepsilonRI to the Rac1-JNK pathway.''; PubMed Europe PMC Scholia
  107. Okamura H, Aramburu J, García-Rodríguez C, Viola JP, Raghavan A, Tahiliani M, Zhang X, Qin J, Hogan PG, Rao A.; ''Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity.''; PubMed Europe PMC Scholia
  108. Whitman M, Downes CP, Keeler M, Keller T, Cantley L.; ''Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate.''; PubMed Europe PMC Scholia
  109. Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J.; ''The structural basis of the activation of Ras by Sos.''; PubMed Europe PMC Scholia
  110. Allen JD, Jaffer ZM, Park SJ, Burgin S, Hofmann C, Sells MA, Chen S, Derr-Yellin E, Michels EG, McDaniel A, Bessler WK, Ingram DA, Atkinson SJ, Travers JB, Chernoff J, Clapp DW.; ''p21-activated kinase regulates mast cell degranulation via effects on calcium mobilization and cytoskeletal dynamics.''; PubMed Europe PMC Scholia
  111. Manicassamy S, Gupta S, Sun Z.; ''Selective function of PKC-theta in T cells.''; PubMed Europe PMC Scholia
  112. Rueda D, Thome M.; ''Phosphorylation of CARMA1: the link(er) to NF-kappaB activation.''; PubMed Europe PMC Scholia
  113. McKay MM, Morrison DK.; ''Integrating signals from RTKs to ERK/MAPK.''; PubMed Europe PMC Scholia
  114. Asada H, Ishii N, Sasaki Y, Endo K, Kasai H, Tanaka N, Takeshita T, Tsuchiya S, Konno T, Sugamura K.; ''Grf40, A novel Grb2 family member, is involved in T cell signaling through interaction with SLP-76 and LAT.''; PubMed Europe PMC Scholia
  115. Wen R, Jou ST, Chen Y, Hoffmeyer A, Wang D.; ''Phospholipase C gamma 2 is essential for specific functions of Fc epsilon R and Fc gamma R.''; PubMed Europe PMC Scholia
  116. Uren AG, O'Rourke K, Aravind LA, Pisabarro MT, Seshagiri S, Koonin EV, Dixit VM.; ''Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma.''; PubMed Europe PMC Scholia
  117. Sakurai H, Miyoshi H, Mizukami J, Sugita T.; ''Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1.''; PubMed Europe PMC Scholia
  118. Yan M, Dai T, Deak JC, Kyriakis JM, Zon LI, Woodgett JR, Templeton DJ.; ''Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1.''; PubMed Europe PMC Scholia
  119. Deckert M, Tartare-Deckert S, Couture C, Mustelin T, Altman A.; ''Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product.''; PubMed Europe PMC Scholia
  120. Kovárová M, Tolar P, Arudchandran R, Dráberová L, Rivera J, Dráber P.; ''Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation.''; PubMed Europe PMC Scholia
  121. Glover JN, Harrison SC.; ''Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA.''; PubMed Europe PMC Scholia
  122. Pribluda VS, Pribluda C, Metzger H.; ''Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation.''; PubMed Europe PMC Scholia
  123. Sebban-Benin H, Pescatore A, Fusco F, Pascuale V, Gautheron J, Yamaoka S, Moncla A, Ursini MV, Courtois G.; ''Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti.''; PubMed Europe PMC Scholia
  124. Takeuchi K, Roehrl MH, Sun ZY, Wagner G.; ''Structure of the calcineurin-NFAT complex: defining a T cell activation switch using solution NMR and crystal coordinates.''; PubMed Europe PMC Scholia
  125. Yang YJ, Chen W, Carrigan SO, Chen WM, Roth K, Akiyama T, Inoue J, Marshall JS, Berman JN, Lin TJ.; ''TRAF6 specifically contributes to FcepsilonRI-mediated cytokine production but not mast cell degranulation.''; PubMed Europe PMC Scholia
  126. Kyriakis JM, Avruch J.; ''Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update.''; PubMed Europe PMC Scholia
  127. Dráber P, Dráberová L.; ''Lipid rafts in mast cell signaling.''; PubMed Europe PMC Scholia
  128. Lutz C, Nimpf J, Jenny M, Boecklinger K, Enzinger C, Utermann G, Baier-Bitterlich G, Baier G.; ''Evidence of functional modulation of the MEKK/JNK/cJun signaling cascade by the low density lipoprotein receptor-related protein (LRP).''; PubMed Europe PMC Scholia
  129. Cargnello M, Roux PP.; ''Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.''; PubMed Europe PMC Scholia
  130. Thome M, Charton JE, Pelzer C, Hailfinger S.; ''Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT1.''; PubMed Europe PMC Scholia
  131. Liu Y, Graham C, Parravicini V, Brown MJ, Rivera J, Shaw S.; ''Protein kinase C theta is expressed in mast cells and is functionally involved in Fcepsilon receptor I signaling.''; PubMed Europe PMC Scholia
  132. Besse A, Lamothe B, Campos AD, Webster WK, Maddineni U, Lin SC, Wu H, Darnay BG.; ''TAK1-dependent signaling requires functional interaction with TAB2/TAB3.''; PubMed Europe PMC Scholia
  133. Kihara H, Siraganian RP.; ''Src homology 2 domains of Syk and Lyn bind to tyrosine-phosphorylated subunits of the high affinity IgE receptor.''; PubMed Europe PMC Scholia
  134. Luo C, Shaw KT, Raghavan A, Aramburu J, Garcia-Cozar F, Perrino BA, Hogan PG, Rao A.; ''Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import.''; PubMed Europe PMC Scholia
  135. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  136. Rawlings DJ, Scharenberg AM, Park H, Wahl MI, Lin S, Kato RM, Fluckiger AC, Witte ON, Kinet JP.; ''Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases.''; PubMed Europe PMC Scholia
  137. Sundarrajan M, Boyle DL, Chabaud-Riou M, Hammaker D, Firestein GS.; ''Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNK.''; PubMed Europe PMC Scholia
  138. Israël A.; ''The IKK complex, a central regulator of NF-kappaB activation.''; PubMed Europe PMC Scholia
  139. Kimura T, Kihara H, Bhattacharyya S, Sakamoto H, Appella E, Siraganian RP.; ''Downstream signaling molecules bind to different phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) peptides of the high affinity IgE receptor.''; PubMed Europe PMC Scholia
  140. Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T.; ''Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors.''; PubMed Europe PMC Scholia
  141. Kim HL, Vander Griend DJ, Yang X, Benson DA, Dubauskas Z, Yoshida BA, Chekmareva MA, Ichikawa Y, Sokoloff MH, Zhan P, Karrison T, Lin A, Stadler WM, Ichikawa T, Rubin MA, Rinker-Schaeffer CW.; ''Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.''; PubMed Europe PMC Scholia
  142. Kawakami Y, Yao L, Miura T, Tsukada S, Witte ON, Kawakami T.; ''Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking.''; PubMed Europe PMC Scholia
  143. Matsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B, Chen Y, Wang D, Lin X.; ''Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation.''; PubMed Europe PMC Scholia
  144. Koyasu S.; ''The role of PI3K in immune cells.''; PubMed Europe PMC Scholia
  145. Wu LC.; ''Immunoglobulin E receptor signaling and asthma.''; PubMed Europe PMC Scholia
  146. Chen ZJ, Parent L, Maniatis T.; ''Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity.''; PubMed Europe PMC Scholia
  147. Wang X, Nadarajah B, Robinson AC, McColl BW, Jin JW, Dajas-Bailador F, Boot-Handford RP, Tournier C.; ''Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death.''; PubMed Europe PMC Scholia
  148. Ainbinder E, Bergelson S, Pinkus R, Daniel V.; ''Regulatory mechanisms involved in activator-protein-1 (AP-1)-mediated activation of glutathione-S-transferase gene expression by chemical agents.''; PubMed Europe PMC Scholia
  149. Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K.; ''TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114731view16:21, 25 January 2021ReactomeTeamReactome version 75
113175view11:24, 2 November 2020ReactomeTeamReactome version 74
112403view15:34, 9 October 2020ReactomeTeamReactome version 73
101307view11:19, 1 November 2018ReactomeTeamreactome version 66
100844view20:51, 31 October 2018ReactomeTeamreactome version 65
100385view19:25, 31 October 2018ReactomeTeamreactome version 64
99932view16:09, 31 October 2018ReactomeTeamreactome version 63
99487view14:41, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99139view12:40, 31 October 2018ReactomeTeamreactome version 62
93828view13:39, 16 August 2017ReactomeTeamreactome version 61
93378view11:22, 9 August 2017ReactomeTeamreactome version 61
87447view13:46, 22 July 2016MkutmonOntology Term : 'Fc epsilon receptor mediated signaling pathway' added !
86464view09:18, 11 July 2016ReactomeTeamreactome version 56
83375view11:03, 18 November 2015ReactomeTeamVersion54
81548view13:05, 21 August 2015ReactomeTeamVersion53
77017view08:31, 17 July 2014ReactomeTeamFixed remaining interactions
76722view12:08, 16 July 2014ReactomeTeamFixed remaining interactions
76048view10:10, 11 June 2014ReactomeTeamRe-fixing comment source
75757view11:25, 10 June 2014ReactomeTeamReactome 48 Update
75107view14:05, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74754view08:50, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADPMetaboliteCHEBI:16761 (ChEBI)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Active CalmodulinComplexREACT_3178 (Reactome)
Allergin

p-LYN p-FCERI

IgE aggregate		ComplexREACT_165244 (Reactome)
AllerginREACT_164121 (Reactome)
BCL10 MALT1ComplexREACT_165506 (Reactome)
BCL10 ProteinO95999 (Uniprot-TrEMBL)
BCL10ProteinO95999 (Uniprot-TrEMBL)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
CALM1ProteinP62158 (Uniprot-TrEMBL)
CARD11ProteinQ9BXL7 (Uniprot-TrEMBL)
CHUK ProteinO15111 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calcineurin Calmodulin ComplexREACT_119482 (Reactome)
Calcineurin ComplexREACT_119672 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

SYK		ComplexREACT_165178 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		ComplexREACT_165068 (Reactome)
DAG

p-5Y-PKC-theta

CBM complex		ComplexREACT_165355 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

TRAF6 oligomer		ComplexREACT_164024 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

TRAF6		ComplexREACT_164811 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer oligo-K63-poly Ub-TRAF6 TAK1 TAB1

TAB2/3		ComplexREACT_165256 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer oligo-K63-poly Ub-TRAF6

activated TAK1 complex		ComplexREACT_164823 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

oligo-K63-poly Ub-TRAF6		ComplexREACT_165243 (Reactome)
DAG

p-5Y-PKC-theta

CBM oligomer		ComplexREACT_165009 (Reactome)
DAG

p-5Y-PKC-theta

p-S552,S645-CARMA1 oligomer		ComplexREACT_164911 (Reactome)
DAG

p-5Y-PKC-theta

p-S552,S645-CARMA1		ComplexREACT_164769 (Reactome)
DAGs MetaboliteCHEBI:18035 (ChEBI)
DAGsMetaboliteCHEBI:18035 (ChEBI)
FCER1A ProteinP12319 (Uniprot-TrEMBL)
FCER1G ProteinP30273 (Uniprot-TrEMBL)
FCERI

IgE

allergin aggregate		ComplexREACT_164529 (Reactome)
FCERI IgEComplexREACT_164240 (Reactome)
FOSProteinP01100 (Uniprot-TrEMBL)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
GAB2 ProteinQ9UQC2 (Uniprot-TrEMBL)
GAB2ProteinQ9UQC2 (Uniprot-TrEMBL)
GADS SLP76ComplexREACT_147999 (Reactome)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRAP2 ProteinO75791 (Uniprot-TrEMBL)
GRB2 SOS1ComplexREACT_4435 (Reactome)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HRASProteinP01112 (Uniprot-TrEMBL)
IMetaboliteCHEBI:16595 (ChEBI)
IGHEProteinP01854 (Uniprot-TrEMBL)
IGHV7-81ProteinQ6PIL0 (Uniprot-TrEMBL)
IGHVProteinA2KUC3 (Uniprot-TrEMBL)
IGKCProteinP01834 (Uniprot-TrEMBL)
IGKV1-5ProteinP01602 (Uniprot-TrEMBL)
IGKV4-1ProteinP06312 (Uniprot-TrEMBL)
IGKVA18ProteinA2NJV5 (Uniprot-TrEMBL)
IGLC1ProteinP0CG04 (Uniprot-TrEMBL)
IGLC2ProteinP0CG05 (Uniprot-TrEMBL)
IGLC3ProteinP0CG06 (Uniprot-TrEMBL)
IGLC6ProteinP0CF74 (Uniprot-TrEMBL)
IGLC7ProteinA0M8Q6 (Uniprot-TrEMBL)
IGLV1-36ProteinQ5NV67 (Uniprot-TrEMBL)
IGLV1-40ProteinQ5NV69 (Uniprot-TrEMBL)
IGLV1-44ProteinQ5NV81 (Uniprot-TrEMBL)
IGLV10-54ProteinQ5NV86 (Uniprot-TrEMBL)
IGLV11-55ProteinQ5NV87 (Uniprot-TrEMBL)
IGLV2-11ProteinQ5NV84 (Uniprot-TrEMBL)
IGLV2-18ProteinQ5NV65 (Uniprot-TrEMBL)
IGLV2-23ProteinQ5NV89 (Uniprot-TrEMBL)
IGLV2-33ProteinQ5NV66 (Uniprot-TrEMBL)
IGLV3-12ProteinQ5NV85 (Uniprot-TrEMBL)
IGLV3-16ProteinQ5NV64 (Uniprot-TrEMBL)
IGLV3-22ProteinQ5NV75 (Uniprot-TrEMBL)
IGLV3-25ProteinQ5NV90 (Uniprot-TrEMBL)
IGLV3-27ProteinQ5NV91 (Uniprot-TrEMBL)
IGLV4-3ProteinQ5NV61 (Uniprot-TrEMBL)
IGLV4-60ProteinQ5NV79 (Uniprot-TrEMBL)
IGLV4-69ProteinQ5NV92 (Uniprot-TrEMBL)
IGLV5-37ProteinQ5NV68 (Uniprot-TrEMBL)
IGLV5-45ProteinQ5NV82 (Uniprot-TrEMBL)
IGLV7-43ProteinQ5NV80 (Uniprot-TrEMBL)
IGLV7-46ProteinQ5NV83 (Uniprot-TrEMBL)
IGLV8-61ProteinQ5NV62 (Uniprot-TrEMBL)
IGLVProteinA2NXD2 (Uniprot-TrEMBL)
IKBKB ProteinO14920 (Uniprot-TrEMBL)
IKBKG ProteinQ9Y6K9 (Uniprot-TrEMBL)
IKKA

IKKB

NEMO		ComplexREACT_7693 (Reactome)
IP3 receptor IP3 complexComplexREACT_12249 (Reactome)
IP3 receptor homotetramerComplexREACT_12247 (Reactome)
ITPR1 ProteinQ14643 (Uniprot-TrEMBL)
ITPR2 ProteinQ14571 (Uniprot-TrEMBL)
ITPR3 ProteinQ14573 (Uniprot-TrEMBL)
Ig heavy chain V-I region EU ProteinP01742 (Uniprot-TrEMBL)
Ig heavy chain V-I region HG3 ProteinP01743 (Uniprot-TrEMBL)
Ig heavy chain V-I region Mot ProteinP06326 (Uniprot-TrEMBL)
Ig heavy chain V-I region ND ProteinP01744 (Uniprot-TrEMBL)
Ig heavy chain V-I region SIE ProteinP01761 (Uniprot-TrEMBL)
Ig heavy chain V-I region WOL ProteinP01760 (Uniprot-TrEMBL)
Ig heavy chain V-II region ARH-77 ProteinP06331 (Uniprot-TrEMBL)
Ig heavy chain V-II region COR ProteinP01815 (Uniprot-TrEMBL)
Ig heavy chain V-II region DAW ProteinP01816 (Uniprot-TrEMBL)
Ig heavy chain V-II region HE ProteinP01818 (Uniprot-TrEMBL)
Ig heavy chain V-II region MCE ProteinP01817 (Uniprot-TrEMBL)
Ig heavy chain V-II region NEWM ProteinP01825 (Uniprot-TrEMBL)
Ig heavy chain V-II region OU ProteinP01814 (Uniprot-TrEMBL)
Ig heavy chain V-II region SESS ProteinP04438 (Uniprot-TrEMBL)
Ig heavy chain V-II region WAH ProteinP01824 (Uniprot-TrEMBL)
Ig heavy chain V-III region BRO ProteinP01766 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUR ProteinP01773 (Uniprot-TrEMBL)
Ig heavy chain V-III region BUT ProteinP01767 (Uniprot-TrEMBL)
Ig heavy chain V-III region CAM ProteinP01768 (Uniprot-TrEMBL)
Ig heavy chain V-III region DOB ProteinP01782 (Uniprot-TrEMBL)
Ig heavy chain V-III region GA ProteinP01769 (Uniprot-TrEMBL)
Ig heavy chain V-III region GAL ProteinP01781 (Uniprot-TrEMBL)
Ig heavy chain V-III region HIL ProteinP01771 (Uniprot-TrEMBL)
Ig heavy chain V-III region JON ProteinP01780 (Uniprot-TrEMBL)
Ig heavy chain V-III region KOL ProteinP01772 (Uniprot-TrEMBL)
Ig heavy chain V-III region LAY ProteinP01775 (Uniprot-TrEMBL)
Ig heavy chain V-III region NIE ProteinP01770 (Uniprot-TrEMBL)
Ig heavy chain V-III region POM ProteinP01774 (Uniprot-TrEMBL)
Ig heavy chain V-III region TEI ProteinP01777 (Uniprot-TrEMBL)
Ig heavy chain V-III region TIL ProteinP01765 (Uniprot-TrEMBL)
Ig heavy chain V-III region TRO ProteinP01762 (Uniprot-TrEMBL)
Ig heavy chain V-III region TUR ProteinP01779 (Uniprot-TrEMBL)
Ig heavy chain V-III region WAS ProteinP01776 (Uniprot-TrEMBL)
Ig heavy chain V-III region WEA ProteinP01763 (Uniprot-TrEMBL)
Ig heavy chain V-III region ZAP ProteinP01778 (Uniprot-TrEMBL)
Ig kappa chain V region EV15 ProteinP06315 (Uniprot-TrEMBL)
Ig kappa chain V-I region AG ProteinP01593 (Uniprot-TrEMBL)
Ig kappa chain V-I region AU ProteinP01594 (Uniprot-TrEMBL)
Ig kappa chain V-I region BAN ProteinP04430 (Uniprot-TrEMBL)
Ig kappa chain V-I region Bi ProteinP01595 (Uniprot-TrEMBL)
Ig kappa chain V-I region CAR ProteinP01596 (Uniprot-TrEMBL)
Ig kappa chain V-I region DEE ProteinP01597 (Uniprot-TrEMBL)
Ig kappa chain V-I region Daudi ProteinP04432 (Uniprot-TrEMBL)
Ig kappa chain V-I region EU ProteinP01598 (Uniprot-TrEMBL)
Ig kappa chain V-I region Gal ProteinP01599 (Uniprot-TrEMBL)
Ig kappa chain V-I region HK101 ProteinP01601 (Uniprot-TrEMBL)
Ig kappa chain V-I region Hau ProteinP01600 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ka ProteinP01603 (Uniprot-TrEMBL)
Ig kappa chain V-I region Kue ProteinP01604 (Uniprot-TrEMBL)
Ig kappa chain V-I region Lay ProteinP01605 (Uniprot-TrEMBL)
Ig kappa chain V-I region Mev ProteinP01612 (Uniprot-TrEMBL)
Ig kappa chain V-I region Ni ProteinP01613 (Uniprot-TrEMBL)
Ig kappa chain V-I region OU ProteinP01606 (Uniprot-TrEMBL)
Ig kappa chain V-I region Rei ProteinP01607 (Uniprot-TrEMBL)
Ig kappa chain V-I region Roy ProteinP01608 (Uniprot-TrEMBL)
Ig kappa chain V-I region Scw ProteinP01609 (Uniprot-TrEMBL)
Ig kappa chain V-I region WAT ProteinP80362 (Uniprot-TrEMBL)
Ig kappa chain V-I region WEA ProteinP01610 (Uniprot-TrEMBL)
Ig kappa chain V-I region Walker ProteinP04431 (Uniprot-TrEMBL)
Ig kappa chain V-I region Wes ProteinP01611 (Uniprot-TrEMBL)
Ig kappa chain V-II region Cum ProteinP01614 (Uniprot-TrEMBL)
Ig kappa chain V-II region FR ProteinP01615 (Uniprot-TrEMBL)
Ig kappa chain V-II region GM607 ProteinP06309 (Uniprot-TrEMBL)
Ig kappa chain V-II region MIL ProteinP01616 (Uniprot-TrEMBL)
Ig kappa chain V-II region RPMI 6410 ProteinP06310 (Uniprot-TrEMBL)
Ig kappa chain V-II region TEW ProteinP01617 (Uniprot-TrEMBL)
Ig kappa chain V-III region B6 ProteinP01619 (Uniprot-TrEMBL)
Ig kappa chain V-III region CLL ProteinP04207 (Uniprot-TrEMBL)
Ig kappa chain V-III region GOL ProteinP04206 (Uniprot-TrEMBL)
Ig kappa chain V-III region HAH ProteinP18135 (Uniprot-TrEMBL)
Ig kappa chain V-III region HIC ProteinP18136 (Uniprot-TrEMBL)
Ig kappa chain V-III region IARC/BL41 ProteinP06311 (Uniprot-TrEMBL)
Ig kappa chain V-III region NG9 ProteinP01621 (Uniprot-TrEMBL)
Ig kappa chain V-III region POM ProteinP01624 (Uniprot-TrEMBL)
Ig kappa chain V-III region SIE ProteinP01620 (Uniprot-TrEMBL)
Ig kappa chain V-III region Ti ProteinP01622 (Uniprot-TrEMBL)
Ig kappa chain V-III region VG ProteinP04433 (Uniprot-TrEMBL)
Ig kappa chain V-III region VH ProteinP04434 (Uniprot-TrEMBL)
Ig kappa chain V-III region WOL ProteinP01623 (Uniprot-TrEMBL)
Ig kappa chain V-IV region B17 ProteinP06314 (Uniprot-TrEMBL)
Ig kappa chain V-IV region JI ProteinP06313 (Uniprot-TrEMBL)
Ig kappa chain V-IV region Len ProteinP01625 (Uniprot-TrEMBL)
Ig kappa chain V-IV region STH ProteinP83593 (Uniprot-TrEMBL)
Ig lambda chain V region 4A ProteinP04211 (Uniprot-TrEMBL)
Ig lambda chain V-I region BL2 ProteinP06316 (Uniprot-TrEMBL)
Ig lambda chain V-I region EPS ProteinP06888 (Uniprot-TrEMBL)
Ig lambda chain V-I region HA ProteinP01700 (Uniprot-TrEMBL)
Ig lambda chain V-I region MEM ProteinP06887 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEW ProteinP01701 (Uniprot-TrEMBL)
Ig lambda chain V-I region NEWM ProteinP01703 (Uniprot-TrEMBL)
Ig lambda chain V-I region NIG-64 ProteinP01702 (Uniprot-TrEMBL)
Ig lambda chain V-I region VOR ProteinP01699 (Uniprot-TrEMBL)
Ig lambda chain V-I region WAH ProteinP04208 (Uniprot-TrEMBL)
Ig lambda chain V-II region BO ProteinP01710 (Uniprot-TrEMBL)
Ig lambda chain V-II region BOH ProteinP01706 (Uniprot-TrEMBL)
Ig lambda chain V-II region BUR ProteinP01708 (Uniprot-TrEMBL)
Ig lambda chain V-II region MGC ProteinP01709 (Uniprot-TrEMBL)
Ig lambda chain V-II region NEI ProteinP01705 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-58 ProteinP01713 (Uniprot-TrEMBL)
Ig lambda chain V-II region NIG-84 ProteinP04209 (Uniprot-TrEMBL)
Ig lambda chain V-II region TOG ProteinP01704 (Uniprot-TrEMBL)
Ig lambda chain V-II region TRO ProteinP01707 (Uniprot-TrEMBL)
Ig lambda chain V-II region VIL ProteinP01711 (Uniprot-TrEMBL)
Ig lambda chain V-II region WIN ProteinP01712 (Uniprot-TrEMBL)
Ig lambda chain V-III region LOI ProteinP80748 (Uniprot-TrEMBL)
Ig lambda chain V-III region SH ProteinP01714 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Bau ProteinP01715 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Hil ProteinP01717 (Uniprot-TrEMBL)
Ig lambda chain V-IV region Kern ProteinP01718 (Uniprot-TrEMBL)
Ig lambda chain V-IV region MOL ProteinP06889 (Uniprot-TrEMBL)
Ig lambda chain V-IV region X ProteinP01716 (Uniprot-TrEMBL)
Ig lambda chain V-V region DEL ProteinP01719 (Uniprot-TrEMBL)
Ig lambda chain V-VI region AR ProteinP01721 (Uniprot-TrEMBL)
Ig lambda chain V-VI region EB4 ProteinP06319 (Uniprot-TrEMBL)
Ig lambda chain V-VI region NIG-48 ProteinP01722 (Uniprot-TrEMBL)
Ig lambda chain V-VI region SUT ProteinP06317 (Uniprot-TrEMBL)
Ig lambda chain V-VI region WLT ProteinP06318 (Uniprot-TrEMBL)
Ig lambda chain V-VII region MOT ProteinP01720 (Uniprot-TrEMBL)
IgH heavy chain V-III region VH26 precursor ProteinP01764 (Uniprot-TrEMBL)
IkBComplexREACT_12767 (Reactome)
JUNProteinP05412 (Uniprot-TrEMBL)
K63polyUb TRAF6 ProteinQ9Y4K3 (Uniprot-TrEMBL)
K63polyUb-NEMO ProteinQ9Y6K9 (Uniprot-TrEMBL)
K63polyUbREACT_21645 (Reactome)
KRASProteinP01116 (Uniprot-TrEMBL)
LAT-2ProteinO43561-2 (Uniprot-TrEMBL)
LAT2ProteinQ9GZY6 (Uniprot-TrEMBL)
LCP2 ProteinQ13094 (Uniprot-TrEMBL)
LYNProteinP07948 (Uniprot-TrEMBL)
MALT1 ProteinQ9UDY8 (Uniprot-TrEMBL)
MALT1ProteinQ9UDY8 (Uniprot-TrEMBL)
MAP2K4ProteinP45985 (Uniprot-TrEMBL)
MAP2K7ProteinO14733 (Uniprot-TrEMBL)
MAP3K1ProteinQ13233 (Uniprot-TrEMBL)
MAP3K7 ProteinO43318 (Uniprot-TrEMBL)
MAPK8/9/10ProteinREACT_21895 (Reactome)
MS4A2 ProteinQ01362 (Uniprot-TrEMBL)
NF-kB complexComplexREACT_12775 (Reactome)
NF-kB complexComplexREACT_12832 (Reactome)
NFAT

CaN

CaM		ComplexREACT_164084 (Reactome)
NFAT

CaN

CaM		ComplexREACT_164266 (Reactome)
NFKB1ProteinP19838 (Uniprot-TrEMBL)
NFKBIA ProteinP25963 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
PAK dimerComplexREACT_164900 (Reactome)
PAK1 ProteinQ13153 (Uniprot-TrEMBL)
PAK2ProteinQ13177 (Uniprot-TrEMBL)
PDK1 PIP2,PIP3ComplexREACT_12991 (Reactome)
PDPK1 ProteinO15530 (Uniprot-TrEMBL)
PDPK1ProteinO15530 (Uniprot-TrEMBL)
PI3KComplexREACT_4240 (Reactome)
PIMetaboliteCHEBI:16152 (ChEBI)
PIMetaboliteCHEBI:16618 (ChEBI)
PIMetaboliteCHEBI:18348 (ChEBI)
PIK3CA ProteinP42336 (Uniprot-TrEMBL)
PIK3CB ProteinP42338 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIK3R2 ProteinO00459 (Uniprot-TrEMBL)
PIP3 activates AKT signalingPathwayREACT_75829 (Reactome) Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PIP3, PIMetaboliteREACT_12804 (Reactome)
PKC-theta ComplexREACT_13197 (Reactome)
PLC gamma1/2ProteinREACT_120292 (Reactome)
PLCG1ProteinP19174 (Uniprot-TrEMBL)
PLCG2 ProteinP16885 (Uniprot-TrEMBL)
PPP3CA ProteinQ08209 (Uniprot-TrEMBL)
PPP3CBProteinP16298 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PRKCQ ProteinQ04759 (Uniprot-TrEMBL)
PRKQC closed conformationProteinQ04759 (Uniprot-TrEMBL)
Phospho-ERK dimerComplexREACT_12827 (Reactome)
Phosphorylated NFATC1/2/3ProteinREACT_120227 (Reactome)
PiMetaboliteCHEBI:18367 (ChEBI)
RAC1 ProteinP63000 (Uniprot-TrEMBL)
RAC1-GDPComplexREACT_22018 (Reactome)
RAF/MAP kinase cascadePathwayREACT_634 (Reactome) The MAP kinase cascade describes a sequence of phosphorylation events involving serine/threonine-specific protein kinases. Used by various signal transduction pathways, this cascade constitutes a common 'module' in the transmission of an extracellular signal into the nucleus.
RELA ProteinQ04206 (Uniprot-TrEMBL)
RasGRPs

DAG

Ca2+		ComplexREACT_164524 (Reactome)
RasGRPsProteinREACT_165129 (Reactome) Rap1 can be activated by certain GEFs that respond to calcium and diacylglycerol (CalDAG-GEFs).
SHC1-2ProteinP29353-2 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
SYK ProteinP43405 (Uniprot-TrEMBL)
SYK/FYNComplexREACT_164115 (Reactome)
SYKProteinP43405 (Uniprot-TrEMBL)
TAB1

TAB2/TAB3

TAK1		ComplexREACT_21619 (Reactome)
TAB1 ProteinQ15750 (Uniprot-TrEMBL)
TAB2 ProteinQ9NYJ8 (Uniprot-TrEMBL)
TAB3ProteinQ8N5C8 (Uniprot-TrEMBL)
TEC,BTK,ITK,ProteinREACT_165246 (Reactome)
TRAF6 ProteinQ9Y4K3 (Uniprot-TrEMBL)
TRAF6ProteinQ9Y4K3 (Uniprot-TrEMBL)
UBE2N ProteinP61088 (Uniprot-TrEMBL)
UBE2V1 ProteinQ13404 (Uniprot-TrEMBL)
Ub-TRAF6 trimer bound to CBM complexComplexREACT_12752 (Reactome)
Ubc13 UBE2V1ComplexREACT_12995 (Reactome)
VAV1 ProteinP15498 (Uniprot-TrEMBL)
VAV2 ProteinP52735 (Uniprot-TrEMBL)
VAV3 ProteinQ9UKW4 (Uniprot-TrEMBL)
VAVProteinREACT_21165 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
p-10Y-LAT2 ProteinQ9GZY6 (Uniprot-TrEMBL)
p-10Y-LAT2ProteinQ9GZY6 (Uniprot-TrEMBL)
p-10Y-NTAL

p-SHC1 GRB2 SOS

GAB2		ComplexREACT_164708 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2 SOS p-3Y-GAB2

PI3K		ComplexREACT_164935 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2 SOS

p-3Y-GAB2		ComplexREACT_164851 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2

SOS		ComplexREACT_165062 (Reactome)
p-2S-cJUN p-2S,2T-cFOSComplexREACT_21707 (Reactome)
p-2Y-PAKProteinREACT_19490 (Reactome)
p-4Y-PLCG1 ProteinP19174 (Uniprot-TrEMBL)
p-4Y-PLCG2 ProteinP16885 (Uniprot-TrEMBL)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV RAC1-GTP

PAK dimer		ComplexREACT_164313 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV

RAC1-GTP		ComplexREACT_164894 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3

p-VAV		ComplexREACT_164523 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS SLP76

PLCG		ComplexREACT_148415 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS

SLP76		ComplexREACT_148283 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV TEC kinases

PIP3		ComplexREACT_164096 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-2Y-BTK/p-2Y-ITK

PIP3		ComplexREACT_164249 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV

p-2Y-TEC kinases		ComplexREACT_165277 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-TEC kinases

PIP3		ComplexREACT_164842 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1

VAV		ComplexREACT_164209 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76

PLCG		ComplexREACT_147980 (Reactome)
p-5Y-LAT

p-SHC1 GRB2

SOS1		ComplexREACT_148348 (Reactome)
p-5Y-LAT-2 ProteinO43561-2 (Uniprot-TrEMBL)
p-5Y-LAT-2ProteinO43561-2 (Uniprot-TrEMBL)
p-5Y-PKC-theta DAGComplexREACT_165187 (Reactome)
p-6Y-SYK ProteinP43405 (Uniprot-TrEMBL)
p-BCL10 ProteinO95999 (Uniprot-TrEMBL)
p-MAP2K4/p-MAP2K7ProteinREACT_21783 (Reactome)
p-MAPK8/9/10REACT_21549 (Reactome)
p-MAPK8/9/10REACT_22035 (Reactome)
p-S177,S181-IKBKB ProteinO14920 (Uniprot-TrEMBL)
p-S177,S181-IKKB

IKKA

NEMO		ComplexREACT_13373 (Reactome)
p-S177,S181-IKKB

IKKA

pUb-NEMO		ComplexREACT_12853 (Reactome)
p-S243-NFATC2 ProteinQ13469 (Uniprot-TrEMBL)
p-S257,T261-MAP2K4ProteinP45985 (Uniprot-TrEMBL)
p-S257-NFATC1 ProteinO95644 (Uniprot-TrEMBL)
p-S265-NFATC3 ProteinQ12968 (Uniprot-TrEMBL)
p-S271,T275-MAP2K7ProteinO14733 (Uniprot-TrEMBL)
p-S32,S36-NFKBIAProteinP25963 (Uniprot-TrEMBL)
p-S552,S645-CARD11ProteinQ9BXL7 (Uniprot-TrEMBL)
p-S552-CARD11ProteinQ9BXL7 (Uniprot-TrEMBL)
p-S63,S73-JUN ProteinP05412 (Uniprot-TrEMBL)
p-S63,S73-JUNProteinP05412 (Uniprot-TrEMBL)
p-SHC1

GRB2

SOS		ComplexREACT_160377 (Reactome)
p-SYK/p-BTKComplexREACT_165606 (Reactome)
p-T325,T331,S362,S374-FOS ProteinP01100 (Uniprot-TrEMBL)
p-T325,T331,S362,S374-FOSProteinP01100 (Uniprot-TrEMBL)
p-Y113,Y128,Y145-LCP2 ProteinQ13094 (Uniprot-TrEMBL)
p-Y1400,Y1412-MAP3K1ProteinQ13233 (Uniprot-TrEMBL)
p-Y172-VAV2 ProteinP52735 (Uniprot-TrEMBL)
p-Y173-VAV3 ProteinQ9UKW4 (Uniprot-TrEMBL)
p-Y174-VAV1 ProteinP15498 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2 ProteinP29353-2 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2ProteinP29353-2 (Uniprot-TrEMBL)
p-Y396-LYNProteinP07948 (Uniprot-TrEMBL)
p-Y452,Y476,Y584-GAB2 ProteinQ9UQC2 (Uniprot-TrEMBL)
p-Y90,T219,T538,S676,S695-PRKCQ ProteinQ04759 (Uniprot-TrEMBL)
p-Y90-PKC-theta DAGComplexREACT_12758 (Reactome)
p-Y90-PRKCQ ProteinQ04759 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADPArrowREACT_12399 (Reactome)
ADPArrowREACT_163658 (Reactome)
ADPArrowREACT_163664 (Reactome)
ADPArrowREACT_163671 (Reactome)
ADPArrowREACT_163676 (Reactome)
ADPArrowREACT_163685 (Reactome)
ADPArrowREACT_163692 (Reactome)
ADPArrowREACT_163708 (Reactome)
ADPArrowREACT_163713 (Reactome)
ADPArrowREACT_163742 (Reactome)
ADPArrowREACT_163765 (Reactome)
ADPArrowREACT_163791 (Reactome)
ADPArrowREACT_163801 (Reactome)
ADPArrowREACT_163808 (Reactome)
ADPArrowREACT_163847 (Reactome)
ADPArrowREACT_163882 (Reactome)
ADPArrowREACT_163935 (Reactome)
ADPArrowREACT_163949 (Reactome)
ADPArrowREACT_163959 (Reactome)
ADPArrowREACT_163980 (Reactome)
ADPArrowREACT_163987 (Reactome)
ADPArrowREACT_163989 (Reactome)
ADPArrowREACT_163990 (Reactome)
ADPArrowREACT_21251 (Reactome)
ADPArrowREACT_6716 (Reactome)
ADPArrowREACT_6896 (Reactome)
AMPArrowREACT_163920 (Reactome)
ATPREACT_12399 (Reactome)
ATPREACT_163658 (Reactome)
ATPREACT_163664 (Reactome)
ATPREACT_163671 (Reactome)
ATPREACT_163676 (Reactome)
ATPREACT_163685 (Reactome)
ATPREACT_163692 (Reactome)
ATPREACT_163708 (Reactome)
ATPREACT_163713 (Reactome)
ATPREACT_163742 (Reactome)
ATPREACT_163765 (Reactome)
ATPREACT_163791 (Reactome)
ATPREACT_163801 (Reactome)
ATPREACT_163808 (Reactome)
ATPREACT_163847 (Reactome)
ATPREACT_163882 (Reactome)
ATPREACT_163920 (Reactome)
ATPREACT_163935 (Reactome)
ATPREACT_163949 (Reactome)
ATPREACT_163959 (Reactome)
ATPREACT_163980 (Reactome)
ATPREACT_163987 (Reactome)
ATPREACT_163989 (Reactome)
ATPREACT_163990 (Reactome)
ATPREACT_21251 (Reactome)
ATPREACT_6716 (Reactome)
ATPREACT_6896 (Reactome)
Active CalmodulinREACT_163756 (Reactome)
Allergin

p-LYN p-FCERI

IgE aggregate		ArrowREACT_163959 (Reactome)
Allergin

p-LYN p-FCERI

IgE aggregate		REACT_163716 (Reactome)
Allergin

p-LYN p-FCERI

IgE aggregate		mim-catalysisREACT_163671 (Reactome)
AllerginREACT_163837 (Reactome)
BCL10 MALT1REACT_163941 (Reactome)
BCL10REACT_163827 (Reactome)
CALM1REACT_12602 (Reactome)
CARD11REACT_163676 (Reactome)
Ca2+REACT_12602 (Reactome)
Ca2+REACT_163677 (Reactome)
Ca2+REACT_163756 (Reactome)
Calcineurin Calmodulin REACT_163737 (Reactome)
Calcineurin Calmodulin mim-catalysisREACT_163737 (Reactome)
Calcineurin REACT_163756 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

SYK		REACT_163708 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

SYK		mim-catalysisREACT_163708 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		ArrowREACT_163708 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		mim-catalysisREACT_163742 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		mim-catalysisREACT_163791 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		mim-catalysisREACT_163808 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		mim-catalysisREACT_163847 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		mim-catalysisREACT_163935 (Reactome)
DAG

p-5Y-PKC-theta

CBM complex		REACT_163827 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

TRAF6 oligomer		REACT_163920 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

TRAF6 oligomer		mim-catalysisREACT_163920 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

TRAF6		REACT_163631 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer oligo-K63-poly Ub-TRAF6 TAK1 TAB1

TAB2/3		REACT_163664 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer oligo-K63-poly Ub-TRAF6 TAK1 TAB1

TAB2/3		mim-catalysisREACT_163664 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer oligo-K63-poly Ub-TRAF6

activated TAK1 complex		ArrowREACT_163664 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer oligo-K63-poly Ub-TRAF6

activated TAK1 complex		mim-catalysisREACT_163980 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

oligo-K63-poly Ub-TRAF6		ArrowREACT_163920 (Reactome)
DAG

p-5Y-PKC-theta CBM oligomer

oligo-K63-poly Ub-TRAF6		REACT_164005 (Reactome)
DAG

p-5Y-PKC-theta

CBM oligomer		REACT_163727 (Reactome)
DAG

p-5Y-PKC-theta

p-S552,S645-CARMA1 oligomer		REACT_163941 (Reactome)
DAG

p-5Y-PKC-theta

p-S552,S645-CARMA1		ArrowREACT_163676 (Reactome)
DAG

p-5Y-PKC-theta

p-S552,S645-CARMA1		REACT_163673 (Reactome)
DAGsArrowREACT_163649 (Reactome)
DAGsREACT_163677 (Reactome)
DAGsREACT_163703 (Reactome)
FCERI

IgE

allergin aggregate		REACT_163959 (Reactome)
FCERI IgEREACT_163837 (Reactome)
FOSREACT_21251 (Reactome)
GAB2REACT_163700 (Reactome)
GADS SLP76REACT_147784 (Reactome)
GDPArrowREACT_147697 (Reactome)
GDPArrowREACT_163939 (Reactome)
GRB2 SOS1REACT_163832 (Reactome)
GTPREACT_147697 (Reactome)
GTPREACT_163939 (Reactome)
H2OREACT_163649 (Reactome)
H2OREACT_163737 (Reactome)
IArrowREACT_12074 (Reactome)
IArrowREACT_163649 (Reactome)
IKKA

IKKB

NEMO		REACT_163980 (Reactome)
IP3 receptor IP3 complexmim-catalysisREACT_12074 (Reactome)
IP3 receptor homotetramerREACT_12008 (Reactome)
IREACT_12008 (Reactome)
IkBREACT_12399 (Reactome)
JUNREACT_6716 (Reactome)
K63polyUbREACT_12553 (Reactome)
K63polyUbREACT_163920 (Reactome)
LAT-2REACT_163808 (Reactome)
LAT2REACT_163935 (Reactome)
LYNREACT_163801 (Reactome)
LYNmim-catalysisREACT_163801 (Reactome)
MALT1REACT_163827 (Reactome)
MAP2K4REACT_163987 (Reactome)
MAP2K7REACT_163949 (Reactome)
MAP3K1REACT_163685 (Reactome)
MAP3K1mim-catalysisREACT_163685 (Reactome)
MAPK8/9/10REACT_6896 (Reactome)
NF-kB complexArrowREACT_12399 (Reactome)
NFAT

CaN

CaM		ArrowREACT_163737 (Reactome)
PAK dimerREACT_163979 (Reactome)
PDPK1REACT_12641 (Reactome)
PI3KREACT_163929 (Reactome)
PIArrowREACT_163990 (Reactome)
PIP3, PIREACT_12641 (Reactome)
PIREACT_163649 (Reactome)
PIREACT_163692 (Reactome)
PIREACT_163700 (Reactome)
PIREACT_163881 (Reactome)
PIREACT_163990 (Reactome)
PKC-theta REACT_163671 (Reactome)
PLC gamma1/2REACT_147817 (Reactome)
PPiArrowREACT_163920 (Reactome)
PRKQC closed conformationREACT_163703 (Reactome)
Phospho-ERK dimermim-catalysisREACT_21251 (Reactome)
Phosphorylated NFATC1/2/3REACT_163737 (Reactome)
PiArrowREACT_163737 (Reactome)
RAC1-GDPREACT_163939 (Reactome)
REACT_12008 (Reactome) The IP3 receptor (IP3R) is an IP3-gated calcium channel. It is a large, homotetrameric protein, similar to other calcium channel proteins such as ryanodine. The four subunits form a 'four-leafed clover' structure arranged around the central calcium channel. Binding of ligands such as IP3 results in conformational changes in the receptor's structure that leads to channel opening.
REACT_12074 (Reactome) IP3 promotes the release of intracellular calcium.
REACT_12399 (Reactome) NF-kB is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins, called IkBs, which mask the nuclear localization signal (NLS) of NF-kB and prevent its nuclear translocation. A key event in NF-kB activation involves phosphorylation of IkB (at sites equivalent to Ser32 and Ser36 of IkB-alpha or Ser19 and Ser22 of IkB-beta) by IKK. The phosphorylated IkB-alpha is recognized by the E3 ligase complex and targeted for ubiquitin-mediated proteasomal degradation, releasing the NF-kB dimer p50/p65 into the nucleus to turn on target genes. (Karin & Ben-Neriah 2000)
REACT_12553 (Reactome) During the phosphorylation of the IKK beta, the regulatory subunit NEMO undergoes K-63-linked polyubiquitination. Ubiquitinated TRAF6 trimer, acts as a E3 ligase and induces this ubiquitination. The ubiquitin target sites in NEMO are not yet clearly identified. Studies of different NF-kB signaling pathways revealed several potential ubiquitination sites on NEMO (e.g., K285, K277, K309 and K399) (Fuminori et al. 2009).
REACT_12602 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
REACT_12641 (Reactome) PI3K activation results in recruitment of the serine/threonine kinase PDK1, (3-phosphoinositide-dependent kinase 1) to the plasma membrane where PDK1 subsequently phosphorylates and activates AKT. PDK1 with its PH domain binds to either PIP3 or PIP2 and is translocated to the plasma membrane. PDK1 seems to exist in an active, phosphorylated configuration under basal conditions (Vanhaesebroeck & Alessi 2000).
REACT_147697 (Reactome) GRB2-bound SOS promotes the formation of active GTP-bound RAS. This activates the mitogen-activated protein kinase (MAPK) cascade, leading to cell growth and differentiation.
REACT_147717 (Reactome) GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). Following phosphorylation of LAT, the GRB2:SOS complex binds to the phosphorylated tyrosines and is thereby translocated to the inner face of the plasma membrane where inactive RAS:GDP resides. The three distal tyrosines, Y171, Y191 and Y226 of LAT are responsible for GRB2 association (Balagopalan et al. 2010, Zhang et al. 2000).
REACT_147784 (Reactome) Gads/GRAP2 (GRB2-related adapter protein 2) is member of the GRB2 adaptor family with a central SH2 domain and linker region flanked by amino- and carboxy-terminal SH3 domains. SLP-76 associates constitutively via its central 20-amino acid proline-rich domain with the C-terminal SH3 domain of Gads, which recruits it to LAT following receptor stimulation. Upon LAT phosphorylation, Gads:SLP-76 complex principally binds to phosphorylated LAT tyrosine 191, with a reduced amount of binding to phosphorylated tyrosine 171 and no interaction with phosphorylated tyrosines 132 or 226 (Houtman et al. 2004, Zhu et al. 2003). Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways (Liu et al. 1999). The LAT-Gads-SLP-76 complex creates a platform for the recruitment of multiple signaling molecules, including PLCgamma1, GRB2, NCK, Rho GEFs, VAV and the Tec-family kinases ITK and BTK (Liu et al. 1999 & 2001, Asada et al. 1999, Yablonski et al. 2001).
REACT_147817 (Reactome) The phospholipase PLC-gamma is an important mediator of TCR, FCERI and DAP12 signal transduction. PLC-gamma hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) and in-turn promotes the Ca+2 influx and activation of NFAT. Activation of PLC-gamma1 entails the binding of PLC-gamma1 to both LAT and SLP-76 adapter proteins. The amino-terminal SH2 domain of PLC-gamma1 was shown to preferentially bind phosphorylated LAT Y132 with high affinity and no detectable binding to phosphorylated tyrosines 171, 191, and 226. PLC-gamma1 was also shown to bind the adapter protein SLP-76 indirectly through GADS, which is bound to LAT at Y171 and Y191. SH3 domain of PLC-gamma1 associates with the proline-rich region of SLP-76 (Yablonski et al. 2001). PLC-gamma1 associates with Gads/SLP-76 complex before binding to p-Y132 of LAT (Houtman et al. 2005). PLC-gamma1 association with LAT is stabilized by Gads/SLP-76 bound to LAT (Zhu et al.2003). Association of PLC-gamma to LAT and SLP-76 couples it to the kinases (Syk and Tec family kinase) required for tyrosine phosphorylation and activation of PLC-gamma.
Mast cells express both PLC-gamma1 and PLC-gamma2 isoforms, which are phosphorylated by BTK/ITK and/or SYK. FCERI-dependent Ca2+ release requires the recruitment of PLC-gamma by SLP-76 and LAT. In mast cells, increased intracellular calcium triggers rapid release of preformed mediators, through a process of vesicle exocytosis, known as degranulation.
Recruitment and activation of phospholipase C gamma (PLC-gamma) is involved in DAP12 signal transduction. Phosphorylation of multiple substrates including PLC-gamma1 has been observed in Ly49D/DAP12 triggered NK cells (McVicar et al. 1998). In myeloid cells, PLC-gamma2 is recruited and then phosphorylated upon activation of TREM2 and DAP12 (Peng et al. 2010).
REACT_163631 (Reactome) BCL10-MALT1 oligomers bind to TRAF6 and this inturn promotes the oligomerization of TRAF6 and activates its E3 ligase activity (Sun et al. 2004).
REACT_163649 (Reactome) Phosphoinositol 4,5-bisphosphate (PIP2) is cleaved in to two most important second messengers diacylglycerol (DAG) and Inositol 1,4,5-triphosphate (IP3) by phospholipase C (PLC). DAG remains within the membrane and activates protein kinase C (PKC) while IP3 leaves the cell membrane and binds to IP3 receptor that releases Ca2+ from endoplasmic reticulum (ER).
REACT_163650 (Reactome) Dephosphorylated NFAT-calcineurin (CaN) complex translocates to nucleus, where it activates transcription of several cytokine genes (e.g..IL2).
REACT_163658 (Reactome) Upon dimer disassociation PAK1 autophosphorylates in both cis- and trans- manner. Serine 144 (S144) in the GTPase-binding domain and threonine 423 (T423) in the activation loop are the target sites for autophosphorylation (Parrini et al. 2002).
REACT_163664 (Reactome) Binding of TAB2 and TAB3 to K63-linked polyubiquitin chains leads to the activation of TAK1 by an uncertain mechanism. Phosphorylation of TAK1 within the activation loop of the kinase is absolutely required for TAK1 activity. TAB1 is known to augment TAK1 catalytic activity by mediating spontaneous oligomerization and induces autophosphorylation of TAK1 (Kishimoto et al. 2000). The binding of TAB2/3 to polyubiquitinated TRAF6 may facilitate polyubiquitination of TAB2/3 by TRAF6 (Ishitani et al. 2003), which might result in conformational changes within the TAK1 complex that leads to the activation of TAK1. Some biochemical studies revealed that free K63 polyubiquitin chains, which are not conjugated to any cellular protein, can directly activate the TAK1 kinase complex (Xia et al. 2009).
REACT_163671 (Reactome) Raft localized PKC-theta is phosphorylated and is activated. Phosphorylation of both tyrosine and serine-threonine residues is important in the regulation of PKC function. Six phosphorylation sites have been identified on PKC-theta: Y90, T219, T538, S676, S685, and S695. Phosphorylation of Y90 positively regulates NF-AT and NF-kB activation in T-cells. In mast cells Src family members Src and LYN have been shown to be involved in phosphorylating Y90 (Wang et al. 2012, Liu et al. 2001).
REACT_163673 (Reactome) CARMA1 phosphorylation initiates its oligomerization and the coiled-coil (CC) domain of CARMA1 is hypothesized to mediate this clustering (Tanner et al. 2007).
REACT_163676 (Reactome) CARMA1 (CARD11/Caspase recruitment domain-containing protein 11), BCL10 (B-cell lymphoma/leukemia 10) and MALT1 (Mucosa-associated lymphoid tissue lymphoma translocation protein 1)/paracaspase have been identified as signaling components that act downstream of PKC-theta. CARMA1 is a scaffold protein and recruits BCL10, MALT1, PKC and TRAF6 to form a multi protein complex. CARMA1 exists in an inactive conformation in which the linker region binds to and blocks the accessibility of the CARD motif. Upon stimulation S552 and S645 linker residues are phosphorylated by PKC-theta and this may weaken this interaction, inducing an open conformation of CARMA1. Further phosphorylation studies have revealed other phosphorylation sites (S109, S551 and S555) that may also promote activation of CARMA1. Serene/threonine kinases PKC-beta, IKKbeta, HPK1 and CaMKII are involved in triggering CARMA1 activation (Thome et al. 2010, Rueda & Thome 2005). (only phosphorylated S552 and S645 are represented in this reaction)
REACT_163677 (Reactome) Ras guanyl nucleotide-releasing proteins (RasGRPs) are guanyl nucleotide exchange factors (GEFs) that activate Ras ultimately leading to MAPK activation. RasGRPs have a catalytic domain composed of Ras exchange motif (REM) and a CDC25 domain, an atypical pair of EF hands that bind calcium and a DAG-binding C1 domain. After PIP2 hydrolysis, RasGRPs are recruited to the plasma membrane by binding to DAG and calcium (Stone 2011, Liu et al. 2007). Upon T-cell activation RasGRP1 specifically interacts with and activates Ras on Golgi instead of the plasma membrane (Bivona et al. 2003). It remains to be determined whether activation of N-Ras by RasGRP1 in mast cells occurs in the Golgi or the plasma membrane (Liu et al. 2007). RasGRP4 is mast cell specific and is involved in the controls Ras activation.
REACT_163685 (Reactome) FCERI aggregation has been shown to activate JNK as well as protein kinases upstream of JNK, such as MEKK1 (Mitogen-activated protein kinase/ERK Kinase Kinase-1) and JNK kinase (JNKK). PAK has been shown to be the upstream kinase involved in the activation of MEKK1, however no direct phosphorylation of MEKK1 by PAK is observed. Two threonine residues at positions 1400 and 1412 (analogous to 1381 and 1393 in mouse) in the activation loop of MEKK1 between the kinase subdomains VII and VIII are essential for its catalytic activity. The catalytic domain of MEKK1 is able to autophosphorylate these residues, enhancing its own activity.
REACT_163692 (Reactome) Phosphorylation of VAV stimulates its GEF activity for RAC1, and thus it plays an important role in linking FCERI to the RAC1-JNK pathway. VAV exists in an auto-inhibitory state, folded in such a way as to inhibit the GEF activity of its DH domain. This folding is mediated through binding of tyrosines in the acidic domain to the DH domain and through binding of the calponin homology (CH) domain to the C1 region. Activation of VAV may involve three events which relieve this auto-inhibition: phosphorylation of tyrosines in the acidic domain causes them to be displaced from the DH domain; binding of a ligand to the CH domain may cause it to release the C1 domain; binding of the PI3K product PIP3 to the PH domain may alter its conformation (Aghazadeh et al. 2000). VAV is phosphorylated on tyrosine residue (Y174 in VAV1/172 in VAV2/173 in VAV3) in the acidic domain. This is mediated by SYK and Src-family tyrosine kinases (Deckert et al. 1996, Schuebel et al. 1998). Once activated, VAV is involved in the activation of RAC1, PAK1, MEK and ERK and cytokine production.
REACT_163700 (Reactome) NTAL cooperates with LAT in mast cells to activate PI3K pathway and cytokine production through Grb2-associated binding protein 2 (GAB2) (Gonzalez-Espinosa et al. 2003). FCERI aggregation induced translocation of a significant fraction of GAB2 from the cytosol to the plasma membrane by binding GRB2. Two of the proline-rich motifs in GAB2 are binding sites for the SH3 of GRB2. GAB2 is also recruited to plasma membrane by binding to phosphatidylinositol-3,4,5-trisphosphate (PIP3) with its plecstrin homology (PH) domain. GAB2 can be recruited to FCERI indirectly through GRB2 bound SHC1. SHC1 is recruited to the FCERI beta chain through its SH2 domain and becomes tyrosyl-phosphorylated. Phosphorylated SHC provides a docking site for the GRB2 and this in turn recruits GAB2 (Yu et al. 2006). GAB2 and PI3K are required for FCERI-induced granule translocation.
REACT_163703 (Reactome) DAG along with intracellular calcium signals cooperatively to activate PKCs, which then trigger other pathways such as the NF-kB pathway, ultimately leading to mast cell degranulation and cytokine production (Wu 2011). MCs express several Protein kinase C (PKC) isozymes and these kinases are involved in both the activation and termination of the degranulation process. PKC-delta is a negative regulator of FCERI mediated mast cell degranulation, whereas PKC-theta facilitates in degranulation (Leitges et al. 2002, Liu et al. 2001). In response to FCERI activation PKC-theta translocates to membrane by binding to DAG with its C1 domain. PKC-theta exists in two conformations closed/inactive and open/active state. In resting state, PKC-theta is autoinhibited where the pseudosubstrate sequence in the N-terminal regulatory region of PKC-theta forms intramolecular interaction with the substrate-binding region in the catalytic domain. This prevents the catalytic domain gaining access to substrates. The allosteric change of PKC-theta from closed to open state involves two important mechanisms: DAG binding to the C1 domains and autophosphorylation of T538 on the activation loop. Interaction with DAG induces conformational change resulting in the exposure of the activation loop of PKC-theta (Wang et al. 2012, Melowic et al. 2007).
REACT_163708 (Reactome) Multiple sites of phosphorylation are known to exist in SYK, which both regulate its activity and also serve as docking sites for other proteins. Some of these sites include Y131 of interdomain A, Y323, Y348, and Y352 of interdomain B, and Y525 and Y526 within the activation loop of the kinase domain and Y630 in the C-terminus (Zhang et al. 2002, Lupher et al. 1998, Furlong et al. 1997). Phosphorylation of these tyrosine residues disrupts autoinhibitory interactions and results in kinase activation even in the absence of phosphorylated ITAM tyrosines (Tsang et al. 2008). SYK is primarily phosphorylated by Src family kinases and this acts as an initiating trigger by generating few molecules of activated SYK which are then involved in major SYK autophosphorylation (Hillal et al. 1997).
REACT_163712 (Reactome) VAV an activator of RAC-GTPases, is redistributed to plasma membrane and is phosphorylated following engagement of FCERI. Phosphorylated SLP-76 tyrosines Y113 and Y128 (112Y and 128Y in mouse) provide binding sites for the SH2 domains of VAV. The binding of VAV to these phosphotyrosine residues may link SLP-76 to the Jun amino-terminal kinase (JNK) pathway and the actin cytoskeleton (Kettner et al. 2003).
In addition to its known role as guanine nucleotide exchange factor (GEF), VAV also modulates cytokine production in mast cells. VAV1-deficient bone marrow-derived mast cells exhibited reduced degranulation and cytokine production and calcium release in addition of reduced activation of c-Jun NH2-terminal kinase 1 (JNK1), although tyrosine phosphorylation of FCERI, SYK and LAT was normal (Manetz et al. 2001, Arudchandran et al. 2000, Song et al. 1999).
REACT_163713 (Reactome) T219, T538 at the activation loop, S676 at the turn motif and S695 at the hydrophobic motif are autophosphorylated in cis-maanner. Posphorylation of T538 is critical for kinase activation and it stabilises the open active conformation. Some studies suggest the involvement of PDK1 (3-phosphoinositide-dependent protein kinase 1) and GLK kinases in the phosphorylation T538.
REACT_163716 (Reactome) Tyrosine phosphorylated ITAM in FCERI gamma subunit serves as docking site for SYK (spleen tyrosine kinases), whereas the beta-subunit ITAM has an extra tyrosine and is shorter than canonical ITAM which makes it unfit to bind SYK. Association of SYK to FCERI gamma-subunit disrupts the COOH-terminal-SH2 interdomain interaction of SYK causing a conformational change opening the molecule leading to its activation (Siraganian et al. 2010, de Castro et al. 2010).
REACT_163727 (Reactome) TRAF6 is a ubiquitin ligase that plays a central role in the IKK-dependent canonical NF-kB pathway. It is recruited to the CBM complex by binding to MALT1. The MALT1 C-terminal Ig domain and extension contain two binding motifs for TRAF6 (Noels et al 2007). After oligomerzation TRAF6, together with Ubc13/Uev1A, activates TAK1 and IKK. It also acts as an E3 ligase for MALT1 and mediates lysine 63-linked ubiquitination (Oeckinghaus et al. 2007).
REACT_163737 (Reactome) Nuclear factor of activated T-cells (NFAT) is a transcription factor which induces genes responsible for cytokine production, for cell-cell interactions etc. NFAT transcription activity is modulated by calcium and Calcineurin concentration. In resting cells NFAT is phosphorylated and resides in the cytoplasm. Phosphorylation sites are located in NFAT's regulatory domain in three different serine rich motifs, termed SRR1, SP2 and SP. Upon stimulation, these serine residues are dephosphorylated by calcineurin, that thought to cause exposure of nuclear localization signal sequences triggering translocation of the dephosphorylated NFAT-CaN complex to the nucleus. Among all the phosphorylation sites one of the site in SRR-2 motif is not susceptable to dephosphorylation by CaN (Takeuchi et al. 2007, Hogan et al. 2003).
REACT_163742 (Reactome) SLP-76 lacks intrinsic catalytic activity and acts as a scaffold, recruiting other proteins for correct localization during molecular signal transduction (Bogin et al. 2007). Activation of FCERI leads to tyrosine phosphorylation of SLP-76 (Gross et al. 1999). SLP-76 has three potential tyrosine phosphorylation sites within its amino terminus region: Y113, Y128, and Y145. Phosphorylation may be mediated by SYK, analogous to the role of ZAP-70 in phosphorylating T-cell SLP-76 (Bubeck-Wardenberg et al. 1996).
REACT_163756 (Reactome) Calcineurin (CaN), also called protein phosphatase 2B (PP2B), is a calcium/Calmodulin (CaM)-dependent serine/threonine protein phosphatase. It exists as a heterodimer consisting of CaM-binding catalytic subunit CaN A chain and a Ca+2 binding regulatory CaN B chain. At low calcium concentrations, CaN exists in an inactive state, where the autoinhibitory domain (AID) binds to the active-site cleft. Upon an increase in calcium concentration CaM binds to Ca+2 ions and gets activated. Active CaM binds to CaN regulatory domain (RD) and this causes release of the AID and activation of the phosphatase (Rumi-Masante et al. 2012). Binding of calcium to CaN B regulatory chain also causes a conformational change of the RD of CaN A chain (Yang & Klee 2000).
REACT_163765 (Reactome) Tyrosine phosphorylation of PLC-gamma enhances its catalytic activity. BTK and SYK are involved in the phosphorylation of PLC-gamma (PLCG). Phosphorylation of tyrosine residues 753, 759, 1197, and 1217 in PLCG2 and 771, 783, and 1254 in PLCG1 have been identified as BTK/SYK-dependent phosphorylation sites.
REACT_163791 (Reactome) SHC is an adapter protein that has been implicated in Ras activation. Mast cells express two isoforms of 46 and 52 kDa. Both isoforms of SHC have two domains, an N-terminal phosphotyrosine-binding (PTB) domain and a C-terminal SH2 domain that allows Shc to bind to proteins containing phosphorylated tyrosine residues. Following receptor stimulation, SHC is phosphorylated by Src kinases Syk on Y239, Y240 and Y317 (p56 isoform). Both phosphotyrosines Y239 and Y317 creates the binding site for the SH2 domain of GRB2.
REACT_163801 (Reactome) LYN localized in lipid rafts undergoes an intermolecular autophosphorylation at tyrosine 396. This residue is present in the activation loop, and its phosphorylation promotes LYN kinase activity.
REACT_163808 (Reactome) LAT is palmitoylated and membrane-associated adaptor protein. It rapidly becomes tyrosine-phosphorylated upon receptor engagement. LAT has nine conserved tyrosine residues of which five have been shown to undergo phosphorylation (Y127, Y132, Y171, Y191 and Y226). Src family kinases, SYK and ZAP-70 efficiently phosphorylate LAT on these tyrosine residues (Jiang & Cheng 2007, Paz et al. 2001). Phosphorylation of LAT creates binding sites for the Src homology 2 (SH2) domain proteins PLC-gamma1, GRB2 and GADS, which indirectly bind SOS, VAV, SLP-76 and ITK (Wange 2000).
REACT_163827 (Reactome) BCL10 and MALT1 proteins form high molecular weight oligomers and only these oligomeric forms can activate IKK in vitro (Sun et al. 2004). BCL10 proteins form homo-oligomers through CARD-CARD interactions whereas in MALT1 the tandem Ig-like domains naturally form oligomers with a tendency towards dimers and tetramers (Dong et al. 2006, Quiu & Dhe-Paganon 2011). These CBM oligomers provides the molecular platform, which can facilitate dimerization or serve as scaffolds on which proteases and kinases involved in NF-kB activation are assembled and activated.
REACT_163832 (Reactome) GRB2 is an adapter protein that contains a central SH2 domain flanked by N- and C-terminal SH3 domains. GRB2 acts downstream of receptor protein-tyrosine kinases and is involved in Ras and MAP kinase pathway activation by associating with the guanine exchange factor (GEF) SOS. GRB2 is constitutively bound to SOS through its SH3 domains, which interact with a proline-rich sequence in the C-terminal part of SOS (Chardin et al. 1993). GRB2-SOS complex binds to phosphotyrosine Y239 and Y317 of SHC1. SHC1 associates with the tyrosine-phosphorylated ITAMs of the FCERI beta-chain and can recruit SOS to membrane. SHC1 and SOS have also been described to associate with LAT via GRB2. Shc binding to Phospho-ITAMs (in vitro binding to phospho peptides) has never been linked to any biological function (activation) and is probably not relevant in a physiological setting.
REACT_163837 (Reactome) FCERI is primarily expressed on mast cells and basophils as a tetrameric complex comprising an IgE-binding alpha subunit, a signal amplifying membrane-tetraspanning beta subunit, and a disulfide-linked gamma chain dimer that provides the receptor its signaling competence (Blank & Rivera 2004). In the absence of an antigen or allergen, FCERI receptor binds to monomeric IgE antibodies, and thus the receptor adopts the antigenic specificity of the prevalent IgE repertoire (Garman et al. 2000). Mast cell activation is initiated when multivalent antigen crosslinks the IgE bound to the high-affinity FCERI, thereby aggregating FCERI (Siraganian 2003). Antigen driven aggregation of FCERI then elicits intracellular signals that result in mast cell exocytosis.
REACT_163841 (Reactome) Upon phosphorylation NATL/LAT2 recruits GRB2:SOS complex into the receptor-signaling complex. Residues Y95, Y118, Y136, Y193, Y233 are the putative GRB2-binding sites on NTAL (Iwaki et al. 2007).
REACT_163847 (Reactome) BTK/ITK are activated in a two step model. In the first step they are recruited to the membrane by binding to PIP3 or, alternatively with other binding partners like SLP-76. Once at the membrane SYK or Src-kinases in the vicinity phosphorylates Y551 (Y512 in ITK) in the activation loop of the catalytic domain of BTK to fully activate it (Rawlings et al. 1996, Park et al. 1996, Kawakami et al. 1994).
REACT_163881 (Reactome) Mast cells express four out of five Tec family members (i.e. BTK, ITK, RLK and TEC) and are activated upon cross-linking of FCERI. They are recruited to the membrane via the interaction of their PH domain with PtdIns(3,4,5)P3 phosphate and their SH2 domain with Y145 of SLP-76 (Kettner et al. 2003). BTK is more important for early response such as phosphorylation of PLC-gamma2 and Ca2+ mobilization, whereas ITK regulates the late responses such as changes in gene expression and cytokine secretion. BTK deficient mice have mild defects in degranulation and severe impairments in the production of proinflammatory cytokines upon FCERI cross-linking (Hata et al. 1998). ITK deficient mice have been reported to have reduced MC degranulation and responses to allergic asthma (Forssell et al. 2005). However, Bone marrow derived mast cells (BMMC) derived from ITK deficient mice display a normal degranulation response but secrete elevated level of cytokines (TNFa and IL-13) (Iyer & August 2008). TEC kinase is also one of the crucial regulators of murine mast cell function. TEC is phosphorylated and activated upon FCERI stimulation. TEC deficient bone marrow derived mast cells did not show any in vitro or in vivo defects in histamine release. However, the generation of the leukotriene LTC4 was severely impaired in the absence of TEC (Schmidt et al. 2009).
REACT_163882 (Reactome) GAB2 have multiple tyrosyl phosphorylation sites that are phosphorylated up on activation of FCERI. SYK is the major tyrosine kinase involved in GAB2 phosphorylation. FYN is also shown to contribute to GAB2 tyrosyl phosphorylation but it is not clear whether GAB2 is a direct substrate of FYN (Yu et al. 2006, Parravicini et al. 2002). GAB2 tyrosines (Y452, Y476 and Y584) in the YXXM motif can be the target phosphorylation sites for SYK/FYN kinases (Chan et al. 2010, Harir et al. 2007).
REACT_163920 (Reactome) TRAF6 possesses ubiquitin ligase activity and undergoes K-63-linked auto-ubiquitination after its oligomerization. In the first step, ubiquitin is activated by an E1 ubiquitin activating enzyme. The activated ubiquitin is transferred to a E2 conjugating enzyme (a heterodimer of proteins Ubc13 and Uev1A) forming the E2-Ub thioester. Finally, in the presence of ubiquitin-protein ligase E3 (TRAF6, a RING-domain E3), ubiquitin is attached to the target protein (TRAF6 on residue Lysine 124) through an isopeptide bond between the C-terminus of ubiquitin and the epsilon-amino group of a lysine residue in the target protein. In contrast to K-48-linked ubiquitination that leads to the proteosomal degradation of the target protein, K-63-linked polyubiquitin chains act as a scaffold to assemble protein kinase complexes and mediate their activation through proteosome-independent mechanisms. This K63 polyubiquitinated TRAF6 activates the TAK1 kinase complex.
REACT_163925 (Reactome) The released NF-kB transcription factor (p50/p65) with unmasked nuclear localization signal (NLS) then moves in to the nucleus. Once in the nucleus, NF-kB binds DNA and regulate the expression of genes encoding cytokines, cytokine receptors, and apoptotic regulators.
REACT_163929 (Reactome) Phosphorylated Y452, Y476, and Y584 of GAB2 binds p85 regulatory subunit of PI3K kinase, resulting in activation of PI3K pathway. PI3K is required for mast cell degranulation and anaphylaxis response but not for cytokine production or contact hypersensitivity (Nishida et al. 2011). Activated PI3K generates second messenger PtdInsP3 (PIP3) at the inner membrane, which provides docking sites for pleckstrin homology (PH) domains of PDK1, AKT and BTK. Activated AKT controls major downstream targets like mTORC1, FOXO3 and GSK3beta pathways that regulate mast cell growth, homeostasis, and cytokine production. BTK triggers PLCgamma2 activation, thereby inducing activation of the transcription factor NFAT and NF-kB.
REACT_163935 (Reactome) NTAL and LAT play complementary roles in the positive regulation of FCERI-mediated degranulation. Upon FCERI aggregation NTAL is phosphorylated by LYN, SYK and KIT on different tyrosines. Phosphorylated NTAL likely contributes to the activation of mast cells by providing docking sites for the recruitment of critical signaling molecules into the lipid raft. There are about ten tyrosines in LAT2 of which five tyrosines principally phosphorylated by SYK are recognised as putative GRB2-binding sites, being part of a YXN motif, whereas LYN and KIT phosphorylate both tyrosines contained in the YXN motifs as well as tyrosines outside of the YXN motifs (Iwaki et al. 2008).
REACT_163939 (Reactome) Rac1 exists in inactive state in the cytosol until the reception of extracellular signals by the cell. To be functional Rac1 is rapidly targeted to the plasma membrane upon cell stimulation. The main factors involved in this mobilisation are the Rac GEFs like VAV and phospholipids (PtdIns(4,5)P2, PtdIns(3,4,5) P3) and lipid rafts at the plasma membrane. VAV catalyses the disassociation of GDP from Rac1 by modifying the nucleotide-binding site such that GDP is released and subsequently replaced. The incoming GTP occupies the nucleotide binding site and finally displaces VAV from Rac1 (Bos et al. 2007, Bustelo et al. 2012).
REACT_163941 (Reactome) Phosphorylation of CARMA1 causes conformational change such that its CARD motif is exposed and is free to interact with BCL10 CARD motif. BCL10 constitutively associated with MALT1 and exists as a preformed complex in the cytoplasm. BCL10 and MALT1 have been identified as key positive regulators of FCERI-dependent NF-kB activation (Klemm et al. 2006). The resulting CARMA1-BCL10-MALT1 (CBM) complex may be stabilized by interactions between the CARMA1 coiled coil (CC) domain and a C-terminal MALT1 region that lacks the DD and first two Ig domains (Thome et al. 2010, Che et al. 2004). The CBM complex transmits activating signals that ultimately result in ubiquitination (Ub) and degradation of the NF-kB inhibitor, IkBa.
REACT_163949 (Reactome) MKK7 is activated by MEKK1 and the residues serine 271 and threonine 275 are the potential phosphorylation sites that are crucial for its kinase activity (phosphorylation sites are based on sequence alignment with MAP kinase kinase family members).
REACT_163959 (Reactome) Upon FCGRI-IgE aggregation, LYN kinase phosphorylates the tyrosine residues within the ITAM (immunoreceptor tyrosine-based activation motifs) of both the beta and gamma subunits. The detailed mechanism of the initial engagement of LYN kinase and FCERI is incompletely understood, but two different models have been proposed. One model postulates that a small fraction of LYN is constitutively bound to beta subunit of FCERI prior to activation. Aggregation of FCERI facilitates the transphosphorylation of one FCERI by LYN bound to a juxtaposed receptor (Vonakis et al. 1997, Draber & Draberova 2002). Alternative model postulates that LYN is observed in lipid rafts enriched in glycosphingolipids, cholesterol, and glycosylphosphatidylinositol-anchored proteins and upon aggregation, FCERI rapidly translocates into lipid rafts, where it is phosphorylated by LYN kinase. Either the association of LYN or FCERI or both with lipid rafts is important for initiating this phosphorylation process (Young et al. 2003, Kovarova et al. 2002, Draber & Draberova 2002).
Beta subunit ITAM differs from canonical ITAMs in two ways; the spacing between the two canonical tyrosines harbours a third tyrosine, and it is one amino acid shorter than in canonical ITAMs, thus making it unfit to bind and recruit Syk. Among the three tyrosine residues (Y219, Y225 and Y229), Y219 may play a predominant role in beta chain function and LYN recruitment. Mutation of this tyrosine would decrease substantially LYN association and subsequent phosphorylation of Y225 and Y229. This would result in decreased gamma phosphorylation and decreased SYK recruitment and activation (On et al. 2004).
REACT_163979 (Reactome) PAK1 kinase is a member of serine/threonine protein kinase family and is widely believed as mediator between Cdc42 and Rac1 and the JNK signal transduction pathway. PAK1 is involved in regulating FCERI mediated mast cell degranulation via effects on calcium mobilisation and cytoskeletal changes (Allen et al. 2009). The conventional PAK family contains a N-terminal conserved Cdc42/Rac-interacting binding domain (CRIB) that overlaps a kinase inhibitory (KI) domain and a C-terminal catalytic domain. PAK1 molecules form trans-inhibited homodimers in which the N-terminal kinase inhibitory (KI) domain of one PAK1 molecule in the dimer binds and inhibits the C-terminal catalytic domain of the other. Isoprenylated Rac1/Cdc42-GTP localized to the membrane recruits PAK1 by binding to the N-terminal CRIB domain. Binding of activated Cdc42/Rac1, breaks the PAK1-dimer and removes the trans-inhibition and stimulates serine/threonine kinase activity of that allows autophosphorylation (Lu & Mayer 1999, Parrini et all. 2009, Zhao et al. 2005).
REACT_163980 (Reactome) In humans, the IkB kinase (IKK) complex serves as the master regulator for the activation of NF-kB by various stimuli. It contains two catalytic subunits, IKK alpha and IKK beta, and a regulatory subunit, IKKgamma/NEMO. The activation of IKK complex is dependent on the phosphorylation of IKK alpha/beta at its activation loop and the K63-linked ubiquitination of NEMO. This basic trimolecular complex is referred to as the IKK complex.
IKK subunits have a N-term kinase domain a leucine zipper (LZ) motifs, a helix-loop-helix (HLH) and a C-ter NEMO binding domain (NBD). IKK catalytic subunits are dimerized through their LZ motifs. IKK beta is the major IKK catalytic subunit for NF-kB activation. Activated TAK1 phosphorylate IKK beta on S177 and S181 (S176 and S180 in IKK alpha) in the activation loop and thus activate the IKK kinase activity, leading to the IkB alpha phosphorylation and NF-kB activation.
REACT_163987 (Reactome) Activated MEKK1 then phosphorylates and activates SAPK/Erk kinase (SEK1), also known as MKK4 or Jun kinase kinase (JNKK) on serine and threonine residues at positions 257 and 261, respectively.
REACT_163989 (Reactome) After initial phosphorylation by SFK's, subsequently Y223 (Y180 in ITK and Y206 in TEC) in the SH3 domain of BTK is autophosphorylated, which may prevent inhibitory intramolecular interactions (Nore et al. 2003, Joseph et al. 2007, Park et al. 1996)
REACT_163990 (Reactome) PI3K catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-triphosphate (PIP3). This PIP3 acts as a membrane anchor for the downstream proteins like PDK1 and AKT.
REACT_164005 (Reactome) K-63 linked polyubiquitin (pUb) chain on TRAF6 provides a scaffold to recruit downstream effector molecules to activate NF-kB. Transforming growth factor beta-activated kinase 1 (TAK1) is a member of the mitogen-activated protein kinase (MAPK) kinase kinase family is shown to be an essential intermediate that transmits the upstream signals from the receptor complex to the downstream MAPKs and to the NF-kB pathway (Broglie et al. 2009). TAK1-binding protein 1 (TAB1), TAB2 and TAB3 constitutively bound to TAK1. TAB1 acts as the activation subunit of the TAK1 complex, aiding in the autophosphorylation of TAK1, whereas TAB2 and its homologue TAB3, act as a adaptors of TAK1 that facilitate the assembly of TAK1 complex to TRAF6. The highly conserved C-terminal zinc finger domain of TAB2 and TAB3 binds preferentially to the K-63-linked polyubiquitin chains on TRAF6 (Broglie et al. 2009, Besse et al. 2007).
REACT_21251 (Reactome) The Fos proteins(c-Fos, FosB, Fra1 and Fra2), which cannot homodimerize, form stable heterodimers with Jun proteins and thereby enhance their DNA binding activity.

On activation of the MAPK pathway, Ser-374 of Fos is phosphorylated by ERK1/2 and Ser-362 is phosphorylated by RSK1/2, the latter kinases being activated by ERK1/2. If stimulation of the MAPK pathway is sufficiently sustained, ERK1/2 can dock on an upstream FTYP amino acid motif, called the DEF domain (docking site for ERKs, FXFP), and phosphorylate Thr-331 and Thr-325.

Phosphorylation at specific sites enhances the transactivating potential of several AP-1 proteins, including Jun and Fos, without having any effect on their DNA binding activities. Thus, phosphorylation of Ser-362 and Ser-374 stabilizes c-Fos but has no demonstrated role in the control of transcriptional activity. On the contrary, phosphorylation of Thr-325 and Thr-331 enhances c-Fos transcriptional activity but has no demonstrated effect on protein turnover.

REACT_21385 (Reactome) c-Jun NH2 terminal kinase (JNK) plays a role in conveying signals from the cytosol to the nucleus, where they associate and activate their target transcription factors.
REACT_21404 (Reactome) The bZIP domains of Jun and Fos form an X-shaped -helical structure, which binds to the palindromic AP-1 site (TGAGTCA) (Glover and Harrison, 1995).
REACT_6716 (Reactome) JNK (c-Jun N-terminal Kinase) phosphorylates several transcription factors including c-Jun after translocation to the nucleus.
REACT_6896 (Reactome) Activated human JNK kinases (MKK4 and MKK7) phosphorylate Thr183 and Tyr185 residues in the characteristic Thr-Pro-Tyr phosphoacceptor loop of each JNK.

JNK is differentially regulated by MKK4 and MKK7 depending on the stimulus. MKK7 is the primary activator of JNK in TNF, LPS, and PGN responses. However, TLR3 cascade requires both MKK4 and MKK7. Some studies reported that in three JNK isoforms tested MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine residue (Thr-183).

RasGRPsREACT_163677 (Reactome)
SHC1-2REACT_163791 (Reactome)
SYK/FYNmim-catalysisREACT_163882 (Reactome)
SYKREACT_163716 (Reactome)
TAB1

TAB2/TAB3

TAK1		REACT_164005 (Reactome)
TEC,BTK,ITK,REACT_163881 (Reactome)
TRAF6REACT_163631 (Reactome)
TRAF6REACT_163727 (Reactome)
Ub-TRAF6 trimer bound to CBM complexmim-catalysisREACT_12553 (Reactome)
Ubc13 UBE2V1ArrowREACT_12553 (Reactome)
Ubc13 UBE2V1ArrowREACT_163920 (Reactome)
Ubc13 UBE2V1REACT_12553 (Reactome)
Ubc13 UBE2V1REACT_163920 (Reactome)
VAVREACT_163712 (Reactome)
p-10Y-LAT2ArrowREACT_163935 (Reactome)
p-10Y-LAT2REACT_163841 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2 SOS

GAB2		REACT_163882 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2 SOS p-3Y-GAB2

PI3K		mim-catalysisREACT_163990 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2 SOS

p-3Y-GAB2		ArrowREACT_163882 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2 SOS

p-3Y-GAB2		REACT_163929 (Reactome)
p-10Y-NTAL

p-SHC1 GRB2

SOS		REACT_163700 (Reactome)
p-2Y-PAKArrowREACT_163658 (Reactome)
p-2Y-PAKArrowREACT_163685 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV RAC1-GTP

PAK dimer		REACT_163658 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV RAC1-GTP

PAK dimer		mim-catalysisREACT_163658 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV

RAC1-GTP		ArrowREACT_163658 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV

RAC1-GTP		ArrowREACT_163939 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3 p-VAV

RAC1-GTP		REACT_163979 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3

p-VAV		ArrowREACT_163692 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3

p-VAV		REACT_163939 (Reactome)
p-5Y-LAT

GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 PIP3

p-VAV		mim-catalysisREACT_163939 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS SLP76

PLCG		REACT_163742 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS

SLP76		REACT_147817 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV TEC kinases

PIP3		REACT_163847 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-2Y-BTK/p-2Y-ITK

PIP3		ArrowREACT_163765 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-2Y-BTK/p-2Y-ITK

PIP3		mim-catalysisREACT_163649 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV

p-2Y-TEC kinases		ArrowREACT_163989 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV

p-2Y-TEC kinases		REACT_163765 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-TEC kinases

PIP3		ArrowREACT_163847 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-TEC kinases

PIP3		REACT_163989 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1 VAV p-TEC kinases

PIP3		mim-catalysisREACT_163989 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1

VAV		REACT_163692 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76 PLCG1

VAV		REACT_163881 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76

PLCG		ArrowREACT_163742 (Reactome)
p-5Y-LAT

p-SHC1 GRB2 SOS1 GADS p-Y113,Y128,Y145-SLP-76

PLCG		REACT_163712 (Reactome)
p-5Y-LAT

p-SHC1 GRB2

SOS1		REACT_147784 (Reactome)
p-5Y-LAT

p-SHC1 GRB2

SOS1		mim-catalysisREACT_147697 (Reactome)
p-5Y-LAT-2ArrowREACT_163808 (Reactome)
p-5Y-LAT-2REACT_147717 (Reactome)
p-5Y-PKC-theta DAGArrowREACT_163713 (Reactome)
p-5Y-PKC-theta DAGREACT_163676 (Reactome)
p-5Y-PKC-theta DAGmim-catalysisREACT_163676 (Reactome)
p-MAP2K4/p-MAP2K7mim-catalysisREACT_6896 (Reactome)
p-MAPK8/9/10ArrowREACT_6896 (Reactome)
p-MAPK8/9/10mim-catalysisREACT_6716 (Reactome)
p-S177,S181-IKKB

IKKA

NEMO		ArrowREACT_163980 (Reactome)
p-S177,S181-IKKB

IKKA

NEMO		REACT_12553 (Reactome)
p-S177,S181-IKKB

IKKA

pUb-NEMO		ArrowREACT_12553 (Reactome)
p-S177,S181-IKKB

IKKA

pUb-NEMO		mim-catalysisREACT_12399 (Reactome)
p-S257,T261-MAP2K4ArrowREACT_163987 (Reactome)
p-S271,T275-MAP2K7ArrowREACT_163949 (Reactome)
p-S32,S36-NFKBIAArrowREACT_12399 (Reactome)
p-S552,S645-CARD11REACT_163673 (Reactome)
p-S63,S73-JUNArrowREACT_6716 (Reactome)
p-S63,S73-JUNREACT_21404 (Reactome)
p-SHC1

GRB2

SOS		REACT_147717 (Reactome)
p-SHC1

GRB2

SOS		REACT_163841 (Reactome)
p-SYK/p-BTKmim-catalysisREACT_163765 (Reactome)
p-T325,T331,S362,S374-FOSArrowREACT_21251 (Reactome)
p-T325,T331,S362,S374-FOSREACT_21404 (Reactome)
p-Y1400,Y1412-MAP3K1ArrowREACT_163685 (Reactome)
p-Y1400,Y1412-MAP3K1mim-catalysisREACT_163949 (Reactome)
p-Y1400,Y1412-MAP3K1mim-catalysisREACT_163987 (Reactome)
p-Y239,Y240,Y317-SHC1-2ArrowREACT_163791 (Reactome)
p-Y239,Y240,Y317-SHC1-2REACT_163832 (Reactome)
p-Y396-LYNArrowREACT_163801 (Reactome)
p-Y396-LYNREACT_163959 (Reactome)
p-Y396-LYNmim-catalysisREACT_163959 (Reactome)
p-Y90-PKC-theta DAGArrowREACT_163671 (Reactome)
p-Y90-PKC-theta DAGREACT_163713 (Reactome)
p21 RAS GDPREACT_147697 (Reactome)
p21 RAS GTPArrowREACT_147697 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP2759"
Personal tools