Fc epsilon receptor (FCERI) signaling (Homo sapiens)

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33, 7224, 6261, 96111, 11877, 8410, 14, 51, 11654, 84, 115, 12110, 103, 11263, 653, 10277, 119, 12321, 50, 1175, 30, 834, 25, 78, 12440, 66, 12118, 23, 1234715, 58, 64, 109609594, 10744, 87, 1256, 17, 312820, 27, 327, 12, 20, 5948, 1057357, 98429734, 53, 120818, 69, 71, 82, 8522, 41, 8829, 56, 60, 67, 68, 9136, 38, 49, 52, 6174, 86, 101, 11011, 1945, 10043, 89, 939, 1041, 9910611435, 37, 55, 75, 1139239, 46, 10847, 7680, 1224, 25, 78, 12426, 70p-5Y-LATp-SHC1GRB2SOS1 CaN-catalytic alpha/beta chains p-5Y-LATp-SHC1GRB2SOS1GADSSLP76PLCG DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6 p-5Y-LATp-SHC1GRB2SOS1 DAGp-5Y-PKC-thetaCBM oligomerTRAF6 oligomer p-SHC1GRB2SOS GADSp-Y113,Y128,Y145-SLP-76 DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6 Immunoglobulin Kappa Light Chain GRB2SOS1 Ig Antibody Light Chain p-5Y-LATp-SHC1GRB2SOS1 Ig Lambda C region TAB1TAB2/TAB3TAK1 PDK1PIP2,PIP3 GADSp-Y113,Y128,Y145-SLP-76 p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2PI3K p-2S-cJUNp-2S,2T-cFOS PIP3, PIAllerginp-LYNp-FCERIIgE aggregate NF-kB complex Ig Heavy Chain V Region DAGp-5Y-PKC-thetaCBM oligomerTRAF6 GADSp-Y113,Y128,Y145-SLP-76 IP3 receptorIP3 complex p-SHC1GRB2SOS PPP3CA/BFe3+Zn2+ p-SHC1GRB2SOS p-10Y-NTALp-SHC1GRB2SOS PLC gamma1/2 DAGp-5Y-PKC-thetaCBM complex p-Y90-PKC-thetaDAG Active Calmodulin NFATCaNCaM Immunoglobulin Lambda Light Chain IgE NF-kB complex p-5Y-PKC-thetaDAG p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG CaN catalytic alpha/betaZn++Fe3+CaMCa2+ p-S177,S181-IKKBIKKANEMO p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-BTK/p-2Y-ITKPIP3 DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6TAK1TAB1TAB2/3 Ig Lambda C region PPP3CA/B p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-TEC kinasesPIP3 p-LYNp-FCERIIgE aggregate p-10Y-NTALp-SHC1GRB2SOS p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76p-PLCG GRB2SOS1 GRB2SOS1 PLC gamma1/2 GRB2SOS1 p-10Y-NTALp-SHC1GRB2SOS CBM oligomerTRAF6 oligomer Ig Antibody Light Chain Active Calmodulin p-5Y-PKC-thetaDAG GRB2SOS1 DAGp-5Y-PKC-thetap-S552,S645-CARMA1 oligomer PPP3CA/BCalmodulin p-SHC1GRB2SOS IgE Heavy Chain Immunoglobulin Lambda Light Chain IgE TAB2/3 p-5Y-LATp-SHC1GRB2SOS1 DAGp-5Y-PKC-thetaCBM oligomer NFATCaNCaM GRB2SOS1 PAK2 dimer PLC gamma1/2 BCL10MALT1 GADSp-Y113,Y128,Y145-SLP-76 PAK dimer Ig Antibody Light Chain Ig Lamda Light Chain V Region p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAV PDK1PIP2,PIP3 PPP3CA/BFe3+Zn2+ p-5Y-LATp-SHC1GRB2SOS1GADSSLP76 PPP3CA/BCalmodulin Ig Kappa Light Chain V Region IgE Heavy Chain p-5Y-PKC-thetaDAG IKKAIKKBNEMO PI3K-catalytic subunit CBM oligomeroligo-K63-poly Ub-TRAF6 oligomer FCERIG dimer p-5Y-LATp-SHC1GRB2SOS1 p-5Y-LATp-SHC1GRB2SOS1 RAC1-GDP IP3 receptors p21 RASGDP RAC1-GTP p-VAV cytosolIg Lamda Light Chain V Region PLC gamma1/2 IP3 receptors p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG TAB1TAB2/TAB3TAK1 p-SHC1GRB2SOS MALT1 trimer Ig Antibody Light Chain Bcl10 trimer bound to CARMA1 trimer p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG Allerginp-LYNp-FCERIIgE aggregate PKC-theta NF-kB complex p-LYNp-FCERIIgE aggregate p-10Y-NTALp-SHC1GRB2SOS CBM oligomer Active Calmodulin CalcineurinCalmodulin p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-TEC kinases p-5Y-PKC-thetaDAG GRB2SOS1 Active Calmodulin p-SHC1GRB2SOS p-5Y-PKC-thetaDAG FCERIIgEallergin aggregate PLC gamma1/2 GRB2SOS1 RAC1-GTP p21 RASGTP GRB2SOS1 Immunoglobulin Kappa Light Chain Immunoglobulin Lambda Light Chain CalcineurinCalmodulin p-PLCG Calcineurin alpha regulatory subunitCalcium Ubc13UBE2V1 Immunoglobulin Kappa Light Chain PPP3CA/B p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG p-VAV p-5Y-LATp-SHC1GRB2SOS1 Immunoglobulin Lambda Light Chain p-SHC1GRB2SOS BCL10 oligomerMALT1 oligomerTRAF6 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG PI3K-regulatory subunit PI3K-regulatory subunit GRB2SOS1 p-SHC1GRB2SOS GADSp-Y113,Y128,Y145-SLP-76 GADSp-Y113,Y128,Y145-SLP-76 PIP3, PIp-5Y-LATp-SHC1GRB2SOS1 p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTP PAK1 dimer GADSSLP76 p-VAV p-CARMA1 oligomerBCL10MALT1 p-5Y-PKC-thetaDAG GADSp-Y113,Y128,Y145-SLP-76 DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6 PI3K-catalytic subunit Clustered pLYNp-FCERIIgEallerginSYK GRB2SOS1 p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2 p-5Y-LATp-SHC1GRB2SOS1 BCL10MALT1 DAGp-5Y-PKC-thetap-S552,S645-CARMA1 GADSp-Y113,Y128,Y145-SLP-76 p-SHC1GRB2SOS PPP3CA/B GRB2SOS1 IgE Ig Lamda Light Chain V Region PLC gamma1/2 CARMA1 trimer p-5Y-PKC-thetaDAG Dephosphorylated NFAT nucleoplasmp-5Y-LATp-SHC1GRB2SOS1GADSSLP76 VAV p-SHC1GRB2SOS PLC gamma1/2 GRB2SOS1 p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTPPAK dimer IkBGRB2SOS1 CBM oligomeroligo-K63-poly Ub-TRAF6 oligomer p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVTEC kinasesPIP3 Ig Lambda C region VAV IgE Heavy Chain VAV Ig Heavy Chain V Region p-SHC1GRB2SOS p-SHC1GRB2SOS Ig Heavy Chain V Region p-5Y-PKC-thetaDAG TAB2/3 p-LYNp-FCERIIgE aggregate IgE GRB2SOS1 p-5Y-LATp-SHC1GRB2SOS1 PI3K p-5Y-LATp-SHC1GRB2SOS1 GADSSLP76 GRB2SOS1 p-5Y-PKC-thetaDAG p-5Y-PKC-thetaDAG p-SHC1GRB2SOS p-5Y-LATp-SHC1GRB2SOS1 Ig Lambda C region CaN catalytic alpha/betaZn++Fe3+ PLC gamma1/2 PLC gamma1/2 GADSp-Y113,Y128,Y145-SLP-76 PI3K p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAV DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6activated TAK1 complex p-SHC1GRB2SOS FCERI MALT1oligomerTRAF6 p21 RAS p21 RAS VAV Dephosphorylated NFATC1/2/3 p-SHC1GRB2SOS CBM oligomeroligo-K63-poly Ub-TRAF6 oligomer p-SHC1GRB2SOS PPP3CA/BFe3+Zn2+ GRB2SOS1 Clustered pLYNp-FCERIIgEallerginp-6Y-SYK CBM oligomerTRAF6 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG FCERIIgE IP3 receptor homotetramer Calcineurin alpha regulatory subunitCalcium Ig Lamda Light Chain V Region CaN alpha regulatoryCa2+ p-SHC1GRB2SOS VAV IP3 receptor homotetramer CaNCaMCa2+ p-10Y-NTALp-SHC1GRB2SOSGAB2 TAB1TAB2/TAB3TAK1 Ub-TRAF6 trimer bound to CBM complex Allerginp-LYNp-FCERIIgE aggregate p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG Ubc13UBE2V1 p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTP TAB2/3 Immunoglobulin Kappa Light Chain RasGRPsDAGCa2+ p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2 Ig Kappa Light Chain V Region Calcineurin GADSSLP76 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG endoplasmic reticulum lumenp-S177,S181-IKKBIKKApUb-NEMO IgE Heavy Chain Ig Heavy Chain V Region MALT1 trimer bound to Bcl10 and CARMA1 trimer Ig Kappa Light Chain V Region Ig Kappa Light Chain V Region GRB2SOS1 IGLV3-22Ig lambda chain V-IV region Bau Ig heavy chain V-I region HG3 RAC1-GDPADPVAV3 Ig lambda chain V-II region NEI VAV2 p-5Y-LAT-2 CALM1 IKBKG PIP3, PICALM1 IGLV1-36BCL10GDP Ig lambda chain V-I region NEWM Ig kappa chain V-II region GM607 Ig kappa chain V-II region MIL Ig heavy chain V-III region BUR p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-TEC kinasesPIP3PIK3R2 DAGsAMPIg heavy chain V-III region BRO Ig lambda chain V-IV region Hil Ig lambda chain V-IV region MOL Ig lambda chain V-III region SH p-5Y-LATp-SHC1GRB2SOS1ADPp-Y90,T219,T538,S676,S695-PRKCQ GRAP2 Ig kappa chain V-II region FR GRB2-1 IGHV7-81PIIg heavy chain V-II region COR DAGs IGLV8-61GRAP2 VAVADPIGLV3-22PLCG1Ig lambda chain V region 4A IGLC2Ig kappa chain V-III region NG9 p-Y173-VAV3 IGKCIg heavy chain V-I region EU Ig heavy chain V-I region WOL Ig kappa chain V-I region EU PAK2Ig lambda chain V-I region NEW Ig lambda chain V-I region NEW IGLC6Ig kappa chain V region EV15 IGLV3-25Ub-TRAF6 trimer bound to CBM complexIg kappa chain V-I region Rei Ig kappa chain V-I region DEE Ig lambda chain V-II region NEI PDPK1p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVATPIg kappa chain V-I region Walker IGLVIg lambda chain V-II region BOH ADPp-Y113,Y128,Y145-LCP2 Ig heavy chain V-III region NIE Ig heavy chain V-III region BUT Ig heavy chain V-III region BUR Ig lambda chain V region 4A p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTPPAK dimerPDPK1 IgH heavy chain V-III region VH26 precursor FOSIg heavy chain V-II region WAH Ig lambda chain V-II region VIL Ig kappa chain V-III region VG Ig kappa chain V-I region Roy CARD11Ig heavy chain V-II region HE Ig kappa chain V-III region WOL IGLV10-54Ig heavy chain V-III region LAY IGLV4-60PPP3CBSOS1 Ig heavy chain V-II region OU ATPLAT-2Ig heavy chain V-II region OU ADPIg heavy chain V-III region LAY p-S552-CARD11Ig heavy chain V-II region HE PKC-theta Ig heavy chain V-III region HIL Ig kappa chain V-I region Wes p-Y90,T219,T538,S676,S695-PRKCQ Ig kappa chain V-II region FR Ig lambda chain V-I region WAH PIK3R1 p-S243-NFATC2 p-Y239,Y240,Y317-SHC1-2 p-Y172-VAV2 ATPIg lambda chain V-VI region NIG-48 ITPR3 Ig kappa chain V-III region HAH Ig kappa chain V-I region OU Zn2+ Ig kappa chain V-I region Lay PIIg kappa chain V-I region Lay K63polyUb TRAF6 UBE2V1 Ig heavy chain V-II region HE Ig heavy chain V-II region HE DAGs Ig kappa chain V-I region Bi Ig kappa chain V-I region AG Ig kappa chain V-I region BAN Ig heavy chain V-I region EU Ig heavy chain V-III region TRO IGLV1-44Ig kappa chain V-II region Cum ADPKRASIg lambda chain V-IV region Bau Ig heavy chain V-II region ARH-77 Ig heavy chain V-III region DOB p-5Y-LAT-2 TAB3DAGp-5Y-PKC-thetaCBM oligomerTRAF6 oligomerIg lambda chain V-I region MEM IGLV2-23Ig lambda chain V-I region NIG-64 Ig lambda chain V-VI region WLT ATPIg kappa chain V-III region HIC Clustered pLYNp-FCERIIgEallerginSYKPIK3CB PLCG2 Ig kappa chain V-III region GOL p-5Y-LAT-2 Ig lambda chain V-II region MGC Ig lambda chain V-II region TRO Ig lambda chain V-VI region AR IGHVATPGRB2SOS1Ig lambda chain V-I region VOR NFKB1Ig kappa chain V-IV region Len Ig lambda chain V-II region MGC PIK3R2 ADPPLCG1PLCG2 Ig kappa chain V-I region EU GTP IGLV3-25Ig heavy chain V-III region GA SOS1 Ig kappa chain V-III region SIE Ig kappa chain V-III region IARC/BL41 ATPGRB2-1 Ig heavy chain V-I region SIE Ig lambda chain V-VI region NIG-48 Ig kappa chain V-I region DEE LAT2Ig kappa chain V-I region Lay TRAF6LCP2 Ig kappa chain V-I region Ka Ig lambda chain V-I region MEM Ig kappa chain V-III region NG9 PIIg kappa chain V-IV region STH Ig kappa chain V-IV region STH DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6TAK1TAB1TAB2/3Ig lambda chain V-III region LOI Ig kappa chain V-III region VG Calcineurin Ig heavy chain V-II region SESS Ig heavy chain V-II region NEWM Ig kappa chain V-I region Ka p-10Y-LAT2 ATPATPp-Y239,Y240,Y317-SHC1-2 IGLV2-11Ig kappa chain V-I region Scw Ig kappa chain V-I region WAT Ig kappa chain V-III region GOL TAB2 Ig lambda chain V-II region NEI IGLV2-11IGHETEC,BTK,ITK,IGLV7-43PLCG1IGLV3-22IGLV3-16Ig lambda chain V-V region DEL PRKQC closed conformationPLCG2 IGLC7Ig heavy chain V-III region ZAP GTPIg lambda chain V-II region TOG Ig heavy chain V-II region ARH-77 p-6Y-SYK ADPIg kappa chain V-I region WEA Fe3+ IGLV3-12p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2PI3KIg heavy chain V-III region POM Ig lambda chain V-I region NEWM Ig kappa chain V-III region HIC Ig kappa chain V-I region DEE Ig heavy chain V-III region TIL p-4Y-PLCG2 p-S177,S181-IKBKB ADPp-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-I region Walker GRB2-1 ADPIGLV7-43Ig lambda chain V-IV region X PLCG1p-Y90,T219,T538,S676,S695-PRKCQ ATPIg heavy chain V-II region NEWM Ig kappa chain V-III region Ti IGLV2-11Ig lambda chain V-II region BOH MALT1 NRAS IGLV10-54IGLV11-55GDPIGLV7-46Ig kappa chain V-I region CAR MAP3K7 VAV2 IGKV4-1IGLC7UBE2V1 Ig lambda chain V-II region TRO Ig heavy chain V-III region TUR Ig heavy chain V-III region TIL Ig kappa chain V-I region Bi Ig kappa chain V-II region GM607 Ig heavy chain V-I region SIE Ig heavy chain V-III region POM Ig kappa chain V-III region CLL Ig heavy chain V-III region TUR p-5Y-LAT-2 IGLV4-3MS4A2 Ig kappa chain V-I region Mev Ig lambda chain V-V region DEL Ig kappa chain V-II region FR Ig kappa chain V-IV region JI ADPDAGs Ig heavy chain V-III region TUR VAV3 DAGs RELA IGLV1-44Ig kappa chain V-I region Scw Ig kappa chain V-III region GOL PLC gamma1/2IGKCADPIg kappa chain V-I region Wes VAV1 p-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-IV region B17 CalcineurinCalmodulin GDPNFATCaNCaMPhosphorylated NFATC1/2/3PIADPIg heavy chain V-III region KOL VAV2 IGLV2-33Ig kappa chain V-I region Ni ADPPIK3CB Ig kappa chain V-I region Gal p-Y239,Y240,Y317-SHC1-2 DAGs IGLV1-36Ig kappa chain V-I region Walker Ig kappa chain V-III region SIE DAGs IGKV1-5Ig heavy chain V-III region BUT Ig heavy chain V-II region COR Ig lambda chain V-I region NIG-64 IGLV3-16Ig kappa chain V-III region HAH CALM1Ig kappa chain V-III region VH MAP3K7 IGLV3-27Ig lambda chain V-IV region Bau IGLV3-25Ig kappa chain V-III region Ti Ig kappa chain V-III region IARC/BL41 Ig kappa chain V-I region CAR Ig lambda chain V-I region NEWM p-Y90,T219,T538,S676,S695-PRKCQ IGLV4-3Ig kappa chain V-II region TEW p-10Y-LAT2p-Y113,Y128,Y145-LCP2 IGLV11-55PIDAGs IGLV1-36Ig lambda chain V-I region HA IGLVIg kappa chain V-I region HK101 p-Y90,T219,T538,S676,S695-PRKCQ Ig kappa chain V-I region Kue p-S265-NFATC3 p-5Y-LAT-2 p-10Y-LAT2 IGLV7-46ATPIGKCADPIg heavy chain V-III region ZAP Ig kappa chain V-I region Hau PPP3CBPIIg lambda chain V-VI region NIG-48 BCL10MALT1Ig lambda chain V-II region TRO BCL10 Ig kappa chain V-I region Mev Ig heavy chain V-III region DOB Ig heavy chain V-II region OU p-Y113,Y128,Y145-LCP2 p-S257-NFATC1 SOS1 Ig lambda chain V-II region TOG Ig kappa chain V region EV15 p-Y90,T219,T538,S676,S695-PRKCQ ADPPPP3CA Ca2+ITPR2 Ig heavy chain V-III region TEI Ig kappa chain V-I region HK101 GRB2-1 p-Y113,Y128,Y145-LCP2 SOS1 Ig heavy chain V-III region GAL IGHEp-S552,S645-CARD11Ig kappa chain V-III region WOL DAGp-5Y-PKC-thetap-S552,S645-CARMA1 oligomerIg kappa chain V-III region HIC Ig heavy chain V-I region SIE Ig heavy chain V-III region JON Ig heavy chain V-III region KOL Ig kappa chain V-I region WAT Ig heavy chain V-III region WEA Ig kappa chain V-III region POM IGLC6Ig kappa chain V-I region Lay Ig heavy chain V-I region EU PPP3R1 p-Y396-LYNIGLVPhospho-ERK dimerIg heavy chain V-III region BUR p-Y173-VAV3 IGHVIg lambda chain V-I region VOR ATPIGLC1SYK/FYNIg heavy chain V-III region JON Ig heavy chain V-II region MCE Active Calmodulinp-Y239,Y240,Y317-SHC1-2 Ig lambda chain V-I region EPS Ig lambda chain V-II region VIL Ig heavy chain V-III region WEA p-BCL10 Ig lambda chain V-VI region SUT Ig kappa chain V-III region HAH IGLV4-69Ig kappa chain V-I region Mev GAB2p-MAP2K4/p-MAP2K7Ig heavy chain V-III region BUT Ig heavy chain V-III region BRO Ig kappa chain V-I region Scw Ig kappa chain V-III region SIE p-S177,S181-IKKBIKKApUb-NEMOIg kappa chain V-I region BAN VAV2 Ig lambda chain V-VII region MOT p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-TEC kinasesCa2+ Ig lambda chain V-I region BL2 CALM1 IGLV3-12Ig heavy chain V-I region ND KRASIGHEIg heavy chain V-II region ARH-77 IGLVp-S265-NFATC3 GRB2-1 VAV3 p-T325,T331,S362,S374-FOSIg lambda chain V-I region HA Ig heavy chain V-II region SESS p-Y239,Y240,Y317-SHC1-2 p-Y239,Y240,Y317-SHC1-2 IGLV2-33GRB2-1 Ig heavy chain V-III region TEI Ig heavy chain V-II region NEWM IGLV4-3Ig heavy chain V-III region GAL IGKCIg lambda chain V region 4A Ig lambda chain V-II region MGC Ig heavy chain V-III region POM Ig lambda chain V-II region TOG PIPLCG1IP3 receptorIP3 complexPPP3R1 Ig lambda chain V-II region VIL LYNIg kappa chain V-I region Wes Ig kappa chain V-I region WEA ATPp21 RASGTPIg lambda chain V-I region NIG-64 Ig heavy chain V-III region WAS MAP3K1Ig heavy chain V-III region TRO SOS1 ATPp-Y173-VAV3 Ig heavy chain V-III region WEA IGLV2-18Ig kappa chain V-I region CAR K63polyUb TRAF6 PRKCQ PIH2OIg heavy chain V-II region DAW IGKVA18Ig kappa chain V-II region TEW p-5Y-LATGRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1PIP3p-VAVRAC1-GTPH2OSOS1 GRAP2 Ig kappa chain V-III region GOL PICa2+ Clustered pLYNp-FCERIIgEallerginp-6Y-SYKADPIg lambda chain V-IV region MOL Ig heavy chain V-III region DOB Ig kappa chain V-I region OU CHUK p-S257-NFATC1 Ig lambda chain V-II region NEI Ig heavy chain V-III region BUR Ig kappa chain V-I region HK101 Ig kappa chain V-III region B6 DAGs Ig lambda chain V region 4A Ig kappa chain V-III region POM Ig lambda chain V-I region NEW IGLV4-69Ig kappa chain V-III region B6 GTP JUNIg heavy chain V-III region CAM Ig lambda chain V-II region NIG-58 IGLV2-11p-Y396-LYNK63polyUbp-S257,T261-MAP2K4PLCG1GRB2-1 VAV1 p-Y113,Y128,Y145-LCP2 Zn2+ IGLV3-25GRB2-1 p-Y1400,Y1412-MAP3K1Fe3+ RasGRPsDAGCa2+RELA DAGp-5Y-PKC-thetaCBM oligomerIg heavy chain V-II region DAW IGLC1Ig lambda chain V-II region TRO Ig lambda chain V-I region EPS Ig heavy chain V-II region MCE p-5Y-LAT-2 SOS1 Ig heavy chain V-I region SIE Ig kappa chain V-I region AU Ig heavy chain V-III region JON p-10Y-NTALp-SHC1GRB2SOSGAB2Ig kappa chain V-I region Daudi Ig kappa chain V-IV region JI Ig heavy chain V-III region WAS PIIg heavy chain V-II region WAH p-2Y-PAKPPP3R1 Ig lambda chain V-I region NIG-64 IGKV1-5Ig heavy chain V-III region GAL Ig heavy chain V-I region Mot IGKV4-1Ig heavy chain V-I region ND Ig heavy chain V-III region LAY Ig lambda chain V-VI region AR SOS1 IGLV3-27PIIg lambda chain V-VI region AR RELA VAV1 PLCG2 NF-kB complexTAB2 Ig kappa chain V-I region EU GRAP2 GRAP2 IGHVIGLV2-23Ig heavy chain V-III region TEI ATPIg heavy chain V-III region CAM ATPGRB2-1 Ig lambda chain V-I region EPS GRAP2 Ig heavy chain V-III region CAM p-Y396-LYNIg heavy chain V-I region HG3 ADPATPIg lambda chain V-VI region SUT IGLV3-12LCP2 p-Y174-VAV1 Ig lambda chain V-III region SH Ig heavy chain V-III region TRO Ig kappa chain V-III region VH Ig lambda chain V-IV region X p-2S-cJUNp-2S,2T-cFOSAllerginp-LYNp-FCERIIgE aggregateIg kappa chain V-I region Kue IGLV3-16Ig kappa chain V-II region GM607 IGHEIGLC6Ig lambda chain V-II region BO Ig kappa chain V-I region DEE IGLV3-27IGLV2-18Ig kappa chain V-I region EU VAV1 Ig heavy chain V-III region LAY Ig lambda chain V-II region NIG-84 p-T325,T331,S362,S374-FOS Ig lambda chain V-VII region MOT HRASIGLV3-27p-Y90-PRKCQ SOS1 Ig kappa chain V-I region Kue RasGRPsK63polyUb TRAF6 PLCG1Ig lambda chain V-I region EPS Ig lambda chain V-II region BO GRB2-1 Ig heavy chain V-III region BUT DAGs Ig kappa chain V-I region CAR p-10Y-LAT2 PIK3CA GADSSLP76Ig kappa chain V-I region Hau Ubc13UBE2V1VAV3 CHUK PPP3CA Ig kappa chain V-I region Roy Ig kappa chain V-II region Cum MALT1 IGLV7-46PiMALT1 Ig kappa chain V-III region VG p-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-I region Gal IGLC2TAB1 Ig kappa chain V-I region Rei Ig heavy chain V-III region WAS p-Y239,Y240,Y317-SHC1-2 Ig kappa chain V region EV15 Ig heavy chain V-III region HIL Ig lambda chain V-II region WIN VAV1 Ig kappa chain V-I region Mev IgH heavy chain V-III region VH26 precursor p-Y113,Y128,Y145-LCP2 p-S32,S36-NFKBIASOS1 Ig kappa chain V-II region Cum TAB3DAGp-5Y-PKC-thetaCBM oligomerTRAF6Ig lambda chain V-I region NEW ADPGRB2-1 Ig kappa chain V-III region POM IGLV11-55p-5Y-LAT-2 IGLC7DAGsATPPPP3CBIg lambda chain V-VI region WLT Ig kappa chain V-I region AU IKKAIKKBNEMOIg heavy chain V-II region ARH-77 p-Y113,Y128,Y145-LCP2 SOS1 Ig lambda chain V-IV region Kern Ig lambda chain V-II region NIG-84 Ig lambda chain V-II region NIG-84 PI3Kp-Y174-VAV1 IGHVPAK dimerIg kappa chain V-I region Ni IGLV3-22FCERIIgEallergin aggregatep-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-Y90,T219,T538,S676,S695-PRKCQ ADPTAB1TAB2/TAB3TAK1p-Y90,T219,T538,S676,S695-PRKCQ Ig kappa chain V-III region SIE Ig lambda chain V-II region MGC Ig heavy chain V-III region KOL IGLV4-69p-5Y-LAT-2 Ig lambda chain V-I region BL2 Ig kappa chain V-I region Daudi PIGRB2-1 NRAS GRB2-1 Ig heavy chain V-III region GA p-Y452,Y476,Y584-GAB2 Ig heavy chain V-I region Mot p-Y396-LYNIg heavy chain V-III region DOB p-S177,S181-IKBKB IGLC1IGLV8-61Ig heavy chain V-III region GA Ig kappa chain V-III region IARC/BL41 DAGp-5Y-PKC-thetap-S552,S645-CARMA1Ig heavy chain V-III region TIL GTPp-S243-NFATC2 Ig kappa chain V-II region RPMI 6410 IGHV7-81ITPR1 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVTEC kinasesPIP3Ig lambda chain V-III region LOI Ig kappa chain V-I region AU Ig kappa chain V-III region WOL Ig kappa chain V-III region IARC/BL41 IGLV8-61Ig kappa chain V-II region MIL Ig kappa chain V-II region RPMI 6410 Ig kappa chain V-II region MIL IGLV1-36Ig kappa chain V-I region Wes IGHV7-81PLCG1RAC1 Ig kappa chain V-III region VG p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCG1VAVp-2Y-BTK/p-2Y-ITKPIP3IKBKG Ig kappa chain V-IV region Len Ca2+PPP3CBp-S552,S645-CARD11IGLV4-69BCL10 Ig lambda chain V-I region VOR p-5Y-LATp-SHC1GRB2SOS1GADSSLP76PLCGIg heavy chain V-III region BRO PIPPP3CA MAP2K7Ig heavy chain V-III region GAL ADPIg kappa chain V-III region Ti DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6activated TAK1 complexCa2+IGLC1Ig kappa chain V-I region Ni p-5Y-LAT-2 Ig kappa chain V-I region Kue Ig lambda chain V-IV region Bau Ig heavy chain V-II region WAH TAB2 ATPIGLV1-40p-MAPK8/9/10Ig lambda chain V-II region NIG-58 DAGs VAV3 PDPK1 Ig kappa chain V-I region Daudi Ig lambda chain V-III region LOI Ig lambda chain V-I region MEM IGLV2-18IP3 receptor homotetramerZn2+ p-Y90-PKC-thetaDAGIg heavy chain V-II region MCE ITPR1 Ubc13UBE2V1Ig lambda chain V-I region MEM Ig lambda chain V-II region NIG-58 Ca2+ p-Y174-VAV1 Ig kappa chain V-I region Bi Ig heavy chain V-I region Mot IGLV5-37ATPADPIg heavy chain V-II region WAH Ig lambda chain V-VI region AR Ig kappa chain V-I region Rei Ig lambda chain V-VII region MOT Ig heavy chain V-II region COR p-10Y-NTALp-SHC1GRB2SOSp-3Y-GAB2ITPR3 SOS1 DAGs IGKV1-5Ig heavy chain V-I region ND Ig lambda chain V-II region BUR NFKB1DAGp-5Y-PKC-thetaCBM complexIg kappa chain V-I region WEA DAGs Ig lambda chain V-III region SH p-Y239,Y240,Y317-SHC1-2 Ig lambda chain V-I region HA IkBFCER1A p-10Y-LAT2 p-5Y-LATp-SHC1GRB2SOS1GADSp-Y113,Y128,Y145-SLP-76PLCGIKBKB Ig kappa chain V-I region Daudi p-5Y-PKC-thetaDAGIGLV5-45p-Y90,T219,T538,S676,S695-PRKCQ IGLV4-60Ig kappa chain V-IV region B17 Ig kappa chain V-I region Hau p-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-I region WEA Ig lambda chain V-IV region Hil IGLV5-45Ig lambda chain V-III region SH GRAP2 NF-kB complexIGLV2-33Ig heavy chain V-III region GA GRAP2 p-10Y-NTALp-SHC1GRB2SOSIg lambda chain V-IV region Kern Ig kappa chain V-III region HIC Ig kappa chain V-II region MIL Ig kappa chain V-I region HK101 Ig heavy chain V-I region WOL IGLV11-55p-Y172-VAV2 p-5Y-LAT-2 Ig kappa chain V-I region AG SHC1-2IGKV4-1IGLV1-44DAGp-5Y-PKC-thetaCBM oligomeroligo-K63-poly Ub-TRAF6FCER1G IGLV5-37Ig heavy chain V-III region HIL Ig kappa chain V-IV region JI Ig lambda chain V-IV region X PLCG2 IgH heavy chain V-III region VH26 precursor Ca2+ Ig heavy chain V-II region DAW Ig kappa chain V-II region GM607 IIg heavy chain V-III region POM GRAP2 SOS1 Ig lambda chain V-VI region EB4 Ig heavy chain V-II region COR p-S63,S73-JUNIg lambda chain V-I region BL2 IGKVA18MALT1Ig kappa chain V-I region Ka Ig kappa chain V-I region BAN PAK1 PIK3CA Ig lambda chain V-IV region MOL Ig lambda chain V-VI region EB4 Ig lambda chain V-I region BL2 Ig heavy chain V-III region TIL NFATCaNCaMPIp-Y239,Y240,Y317-SHC1-2 IGLV2-23SOS1 Ig heavy chain V-I region ND IGLV1-40Ig heavy chain V-III region ZAP Ig lambda chain V-VI region EB4 PLCG2 RAF/MAP kinase cascadeIGLV4-60HRASIGLC7GTP Ig kappa chain V-IV region B17 Ig heavy chain V-III region HIL MAP2K4Ig kappa chain V-I region Scw Ig kappa chain V-I region BAN ADPp-Y113,Y128,Y145-LCP2 PPiIg lambda chain V-II region WIN Ig lambda chain V-I region WAH p21 RASGDPPIIGLV5-45p-Y239,Y240,Y317-SHC1-2 GRB2-1 Ig lambda chain V-II region TOG PLCG2 IGLV7-46Ig kappa chain V-I region AG PIPIP3 activates AKT signalingADPIg heavy chain V-I region HG3 ATPp-S63,S73-JUN Ig kappa chain V-III region B6 ADPIg kappa chain V-I region Roy IGLV10-54IGLV7-43Ig lambda chain V-V region DEL Ig lambda chain V-II region WIN Ig lambda chain V-V region DEL ATPIg heavy chain V-III region WEA SYK IGLV7-43p-Y90,T219,T538,S676,S695-PRKCQ ITPR2 GRAP2 Ig kappa chain V-I region Ka Ig kappa chain V-IV region Len TAB1 IGLC3Ig lambda chain V-I region WAH SOS1 p-5Y-LAT-2 GRB2-1 IGHV7-81Ig kappa chain V-II region RPMI 6410 TAB3Fe3+ RAC1 SYKIg heavy chain V-III region NIE Ig lambda chain V-VI region EB4 Ig kappa chain V-IV region B17 GRB2-1 Ig lambda chain V-IV region MOL Ig lambda chain V-II region BOH Zn2+ ATPIg kappa chain V-III region WOL MAPK8/9/10IGLC6Ig lambda chain V-I region HA Ig kappa chain V-III region B6 VAV2 IGLV1-44Ig kappa chain V-I region Ni Ig kappa chain V-II region TEW INFKB1Ig kappa chain V-II region TEW IGLV3-12GRB2-1 Ig heavy chain V-II region NEWM Ig lambda chain V-I region NEWM p-5Y-LAT-2ADPIg kappa chain V-I region WAT Ig lambda chain V-IV region X Ig kappa chain V-I region Gal p-Y239,Y240,Y317-SHC1-2 p-MAPK8/9/10p-Y239,Y240,Y317-SHC1-2IGKV1-5p-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-I region OU Ig kappa chain V-I region Hau GAB2 Ig kappa chain V-III region VH IGLV5-45IGLV3-16PIIg kappa chain V-II region RPMI 6410 ATPIg lambda chain V-II region BUR IGLC3Ig heavy chain V-III region CAM Ig heavy chain V-I region HG3 Ig heavy chain V-III region JON K63polyUbIg kappa chain V-IV region STH IGLC2Ig kappa chain V-I region AG LCP2 GDP IGKVA18Ig kappa chain V-IV region Len IGLV8-61IgH heavy chain V-III region VH26 precursor ATPIg heavy chain V-III region TUR Ig lambda chain V-IV region Kern IGLV2-18Ig lambda chain V-II region NIG-58 Ig lambda chain V-II region BO ATPPIK3R1 Ca2+ Ig kappa chain V-III region VH Ig kappa chain V-III region NG9 GRB2-1 Ig heavy chain V-III region BRO Ig kappa chain V-II region FR Ig lambda chain V-VI region SUT Fe3+ Ig lambda chain V-II region BOH Ig kappa chain V-III region POM MAP3K7 Ig lambda chain V-VI region WLT PINFKBIA IGKV4-1p-Y113,Y128,Y145-LCP2 UBE2N Ig kappa chain V-III region CLL Ig heavy chain V-II region SESS Ig kappa chain V-I region Rei Ig lambda chain V-IV region Hil GRAP2 Ig lambda chain V-I region WAH IGLV2-33p-SYK/p-BTKIg heavy chain V-I region EU RAC1 Ig heavy chain V-III region NIE Ig kappa chain V-I region Roy IGLV1-40SOS1 Ig lambda chain V-II region NIG-84 p-SHC1GRB2SOSUBE2N PPP3R1 SOS1 Ig kappa chain V-I region Gal ATPIg heavy chain V-III region NIE GRAP2 p-5Y-LATp-SHC1GRB2SOS1GADSSLP76Ig kappa chain V-I region Walker TAB1 Ig lambda chain V-II region VIL IGLV10-54p-Y172-VAV2 Ig lambda chain V-II region BUR Ig heavy chain V-III region ZAP Ig heavy chain V-II region OU Ig kappa chain V-III region CLL Ig lambda chain V-II region BUR Ig kappa chain V-III region HAH PLCG1p-4Y-PLCG1 Ig lambda chain V-VI region NIG-48 Ig kappa chain V-I region AU Ig lambda chain V-I region VOR Ig kappa chain V-IV region JI Ig lambda chain V-IV region Hil CHUK Ig heavy chain V-I region WOL DAGs PPP3CA p-Y452,Y476,Y584-GAB2 Ig kappa chain V-I region OU Ig kappa chain V region EV15 Ig heavy chain V-III region TRO p-5Y-LAT-2 IGLC2IGLC3Ig kappa chain V-IV region STH K63polyUb-NEMO Ig kappa chain V-III region NG9 K63polyUb TRAF6 IGLV1-40PLCG2 AllerginIGLV2-23Ig heavy chain V-III region KOL IGLC3IGKVA18Ig lambda chain V-VI region WLT p-S271,T275-MAP2K7Ig heavy chain V-III region WAS Ig lambda chain V-IV region Kern CALM1 Ig kappa chain V-I region WAT IGLV5-37Ig lambda chain V-II region WIN Ig lambda chain V-VII region MOT FCERIIgETRAF6 Ig lambda chain V-VI region SUT SOS1 Ig kappa chain V-III region CLL Ig heavy chain V-I region WOL Ig lambda chain V-III region LOI Ig kappa chain V-II region Cum IGLV4-3Ig kappa chain V-III region Ti p-S177,S181-IKKBIKKANEMOPIp-Y239,Y240,Y317-SHC1-2 Ig heavy chain V-III region TEI PIIg heavy chain V-II region SESS PLCG2 IGLV4-60IGLV5-37Ig kappa chain V-I region Bi Ig heavy chain V-II region DAW Ig heavy chain V-II region MCE Ig heavy chain V-I region Mot Ig lambda chain V-II region BO PDK1PIP2,PIP328132828132, 161379969013131313132813


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Wikipathways-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).

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  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
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  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
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  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
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  103. Raivich G.; ''c-Jun expression, activation and function in neural cell death, inflammation and repair.''; PubMed Europe PMC Scholia
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  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
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  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
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  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
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  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

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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 signalingPathwayWP2653 (WikiPathways) 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 cascadePathwayWP2735 (WikiPathways) 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_163671 (Reactome)
Allergin

p-LYN p-FCERI

IgE aggregate		REACT_163716 (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 REACT_163756 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

SYK		REACT_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		REACT_163742 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		REACT_163791 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		REACT_163808 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		REACT_163847 (Reactome)
Clustered p

LYN p-FCERI IgE allergin

p-6Y-SYK		REACT_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		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

activated TAK1 complex		ArrowREACT_163664 (Reactome)
DAG

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

activated TAK1 complex		REACT_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 complexREACT_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)
MALT1REACT_163827 (Reactome)
MAP2K4REACT_163987 (Reactome)
MAP2K7REACT_163949 (Reactome)
MAP3K1REACT_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 dimerREACT_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/FYNREACT_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 complexREACT_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		REACT_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		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

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		REACT_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		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_147697 (Reactome)
p-5Y-LAT

p-SHC1 GRB2

SOS1		REACT_147784 (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-MAP2K4/p-MAP2K7REACT_6896 (Reactome)
p-MAPK8/9/10ArrowREACT_6896 (Reactome)
p-MAPK8/9/10REACT_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		REACT_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-BTKREACT_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-MAP3K1REACT_163949 (Reactome)
p-Y1400,Y1412-MAP3K1REACT_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-Y90-PKC-theta DAGArrowREACT_163671 (Reactome)
p-Y90-PKC-theta DAGREACT_163713 (Reactome)
p21 RAS GDPREACT_147697 (Reactome)
p21 RAS GTPArrowREACT_147697 (Reactome)
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