Signaling by the B Cell Receptor (BCR) (Homo sapiens)

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1, 5, 17, 19-21, 24...10, 65, 75, 127, 14911422, 57, 82, 142, 1451, 19, 24, 3027, 31, 41, 47, 50...73, 126, 136, 14634, 52, 68, 70, 88...4, 32, 33, 37, 39...11, 18, 104, 113, 14717, 26, 8535, 36, 83, 97, 128...15, 69, 108, 1378, 12, 6131, 47, 63, 1395, 20, 21, 24, 40...38, 67, 105, 109, 110, 124...5, 20, 24, 54, 76...8, 12, 59, 61, 621, 7, 9, 19, 30...17, 26, 8523, 53, 58, 74, 107...29, 114, 14584, 95, 111, 117, 1196, 49, 79, 91, 115...57, 114, 14213, 89, 94, 98, 12723, 53, 58, 74, 107...IP3 receptor homotetramer STIM1 Dimer CalcineurinPhosphorylated NFATC1/2/3 PPP3CA/BCalmodulin p-BCR NF-kappaB p50c-RelIkB IgM NF-kappaB p65p65 Orai1 dimer STIM1Calcium IgM or IgD NF-kappaB p65p65p-IKB p-SHC1 p46/p52 NF-kappaB p50p50 Immunoglobulin Lambda Light Chain p-CARMA1 Oligomer NF-KappaB p50p50p-IKBA STIM1 Dimer IgD Heavy Chain CARMA1BCL10MALT1TAK1 Ig Lambda C region NF-kB complex IgD NF-kappaB p65p65 Immunoglobulin Kappa Light Chain STIM1TRPC1 Antigenp-BCR CARMA1MALT1BCL10 IgM or IgD Antigenp-BCR IgM Heavy Chain Ig Antibody Light Chain IgD Heavy Chain Ig Antibody Light Chain NF-KappaB p50p50p-IKBA NF-kB complex Immunoglobulin Lambda Light Chain Ig Heavy Chain V Region Ig Lambda C region Ig Kappa Light Chain V Region IgM Heavy Chain NF-kappaB p50c-Relp-IKB Ig Lambda C region Ig Heavy Chain V Region ub-p-IKB alpha/beta/epsilon Ig Lamda Light Chain V Region Ig Antibody Light Chain p-PLC gamma1,2PIP3 IgD NF-kB complex NF-kappaB p50p50 IgM PPP3CA/BFe3+Zn2+ IgD NF-kappaB p50c-Rel NF-kappaBp-IkBSCF-betaTrCP Ig Lambda C region NF-kappaB p50p65ub-p-IKB Antigenp-BCR Immunoglobulin Kappa Light Chain IgD Ig Kappa Light Chain V Region Immunoglobulin Kappa Light Chain Antigenp-BCRp-SYK BCAP Signalosome CARMA1MALT1BCL10 p-BCR IgM or IgD IgM or IgD BCR NF-kappaB p65p65IKB IgD Ig Antibody Light Chain Active IKK complex Ig Lamda Light Chain V Region NF-kappa-B p50/ p65/c-Relp-IKB IgM p-RasGRP1/3 SCF-beta-TrCP2 complex NF-KappaB p50p50ub-p-IKBA CRAC channel Ig Antibody Light Chain Ig Kappa Light Chain V Region NF-kappaB p50p65IKB FKBP1ATacrolimus IP3 receptor homotetramer STIM1 Dimer Active Calmodulin Ig Kappa Light Chain V Region SCF-beta-TrCP2 complex endoplasmic reticulum lumenBLNKGRB2SOS1CIN85CBL SCF-beta-TrCp1/2 PIK3CDPIK3R1 p-IKB alpha/beta/epsilon Ig Heavy Chain V Region Ig Heavy Chain V Region NF-kappaB p50p65p-IKB IP3 receptors Ig Lambda C region Antigenp-BCR IgM p-PLC gamma1/2 Immunoglobulin Kappa Light Chain Ig Lamda Light Chain V Region IgD Heavy Chain p21 RASGTP IgD Heavy Chain NF-kappaB p50p65p-IKB CD19VAV1 PPP3CA/BFe3+Zn2+ NF-kappaB p65p65ub-p-IkB SCF-beta-TrCP1 complex BLNK p-BCR Activated PKC beta Ig Heavy Chain V Region NF-kappaB p65p65 p-CARMA1 Oligomer Immunoglobulin Lambda Light Chain IgM Heavy Chain IgM or IgD NF-kB complex NF-kappaB p50/p65/c-Rel Dimer cytosolIg Antibody Light Chain Immunoglobulin Kappa Light Chain AntigenBCR CARMA1MALT1BCL10 PPP3CA/B PIK3CDPIK3R1 Ig Antibody Light Chain Cyclophilin ACyclosporin A Ig Kappa Light Chain V Region p-RasGRP1,3DAG Immunoglobulin Lambda Light Chain IgD Heavy Chain p-CARMA1 Oligomer NF-kappaB p50c-Rel p21 RAS Ig Lamda Light Chain V Region Antigenp-BCRp-SYK Ig Lambda C region 26S proteasome NF-kB complex NF-kappaB p50c-Rel Immunoglobulin Kappa Light Chain IgD IgM or IgD CalcineurinCalmodulin CD19 Signalosome IgD Heavy Chain Active Calmodulin p21 RAS Immunoglobulin Lambda Light Chain p-BLNKGRB2SOS1CIN85CBL plasma membraneIg Kappa Light Chain V Region NF-kappaB p50/p65/c-Relub-p-IKB p-BAM32PIP3 NF-kappaB p50p50 NF-kappaB p50p50 p-IKB alpha/beta/epsilon NF-kappaB p65p65p-IKB NF-kappaB p65p65 NF-kappaB p50c-Rel Antigenp-BCRp-SYKp-BLNK p21 RASGDP IgM or IgD IgM Heavy Chain Immunoglobulin Lambda Light Chain Antigenp-BCR Ig Kappa Light Chain V Region Ig Heavy Chain V Region CARMA1 oligomer NF-kappaB p50p50 p-BLNKGRB2SOS1CIN85CBL PIK3CDPIK3R1 Ig Heavy Chain V Region NF-kappaB p65p65 IgM Heavy Chain Immunoglobulin Lambda Light Chain IKB alpha/beta/epsilon IgM Calcineurin PPP3CA/B Immunoglobulin Kappa Light Chain IgM Heavy Chain Ig Lamda Light Chain V Region Ig Lamda Light Chain V Region Ig Lambda C region Antigenp-BCRp-SYKp-BLNK IgD Heavy Chain NF-kappaB p50c-Relub-p-IKB Phosphorylated NFATC1/2/3 NF-kappaB p50c-Rel Ig Lamda Light Chain V Region NF-kappa-B p50,/p65,/c-RelIKB NF-KappaB p50p50IKBA NF-kappaB p50p50 NF-kappaB p50/p65/c-Rel Dimer IKKAIKKBNEMO p-BTKPIP3 IgM Antigenp-BCRSYK NF-kappaB p50c-Rel CARMA1BCL10MALT1TAK1IKK IP3 receptors SCF-beta-TrCP1 complex p-CARMA1 Oligomer IgM NF-kappa-B p50/ p65/c-Relp-IKB IgM Heavy Chain BCR Antigenp-BCRp-SYK Calcineurin alpha regulatory subunitCalcium PIK3CDPIK3R1 p-BCR IP3 receptorIP3 complex p-BCR NF-kB complex NF-kappaB p50c-Relp-IKB IgD IKKAIKKBNEMO NF-kappaB p65p65 SCF-beta-TrCp1/2 nucleoplasmOrai1 dimer REL Ig kappa chain V-IV region B17 Ig lambda chain V-III region SH Ig heavy chain V-III region GAL Ig lambda chain V-I region NIG-64 Cyclosporin A p-Y771,Y783-PLCG1 Ig heavy chain V-II region WAH Ig heavy chain V-II region MCE Ig heavy chain V-II region SESS IGLC3IGKCIg kappa chain V-II region Cum IKBKG Ig lambda chain V-IV region Bau Ig kappa chain V-III region NG9 Ig heavy chain V-II region SESS Ig lambda chain V-I region WAH Ig lambda chain V-IV region X Ig kappa chain V-III region IARC/BL41 Ig heavy chain V-III region TIL Ig lambda chain V-VI region NIG-48 Ig heavy chain V-III region NIE p-CARMA1 OligomerIg kappa chain V-III region HIC Ig heavy chain V-III region TRO Ig heavy chain V-II region WAH Ig heavy chain V-I region HG3 Ig heavy chain V-I region ND IGHMIGLC7Ig kappa chain V-I region Ka Ig kappa chain V-I region CAR Ig lambda chain V-IV region X PSMD13 IGLC2Ig heavy chain V-III region WEA IGHVIg heavy chain V-III region JON 26S proteasomeIg heavy chain V-II region COR Ig kappa chain V-I region Lay PSMB6 Ig kappa chain V-III region HIC Ig heavy chain V-III region BRO CBLB IGKV1-5Ig lambda chain V-IV region MOL Ig lambda chain V-VI region WLT ATPIg heavy chain V-II region SESS Ig kappa chain V-I region Wes Ig lambda chain V-I region MEM Ig heavy chain V-III region GA ADPIg heavy chain V-II region ARH-77 Ig kappa chain V-III region HIC p-S157,S161-Ub-NFKBIE CBLB Ig lambda chain V-IV region MOL Ig heavy chain V-I region HG3 Ig heavy chain V-III region ZAP Ig heavy chain V-III region LAY Ig lambda chain V-II region NIG-58 ADPIg kappa chain V-IV region JI Ig heavy chain V-II region COR PSMA6 IGHDIKBKB IGLVp-Y223,Y551-BTK Ig heavy chain V-III region KOL Ig heavy chain V-III region JON Ig lambda chain V-II region BO DAPP1Ig heavy chain V-III region BUR PPP3R1 Ig heavy chain V-I region HG3 Ig heavy chain V-III region ZAP PSMA3 Ig kappa chain V-I region Lay Ig lambda chain V-III region LOI Ig lambda chain V-V region DEL p-S559,S644,S652-CARD11Ig heavy chain V-III region BUT RELA Ig heavy chain V-II region SESS BLKIg lambda chain V-II region BO p-T184-RASGRP1 GRB2-1Ig kappa chain V-IV region Len Active CalmodulinPIK3CD Ig heavy chain V-II region HE Ig kappa chain V-I region DEE Ig lambda chain V-II region BUR Ig heavy chain V-III region KOL Ig lambda chain V-VI region AR Ig lambda chain V-II region MGC Ig heavy chain V-I region WOL Ig heavy chain V-II region OU IGKCIg kappa chain V-III region Ti Ig lambda chain V-V region DEL Ig kappa chain V-III region VH Ig heavy chain V-I region EU NFKB1NF-kappa-B p50,/p65,/c-RelIKBIg lambda chain V-IV region Kern p-Y196,Y207-CD79B Ig heavy chain V-III region GAL Ig kappa chain V-I region Hau BLNK Ig kappa chain V-III region HIC Ig lambda chain V-VI region EB4 ADPIg lambda chain V-II region NIG-84 Ig heavy chain V-II region ARH-77 Ig lambda chain V-II region WIN Ig heavy chain V-III region CAM Ig lambda chain V-I region NEWM Ig kappa chain V-III region VH Ig kappa chain V-I region WAT Ig heavy chain V-III region CAM Ig lambda chain V-I region EPS PIK3R1 Ig heavy chain V-III region BRO Ub-21,22-p-S32,S36-NFKBIA Ig kappa chain V-I region WAT Ig kappa chain V-III region VG Ig kappa chain V-I region Ni TRPC1 Ig kappa chain V-III region NG9 Ig heavy chain V-III region POM Ig kappa chain V-I region EU Ig kappa chain V-I region Bi Ig heavy chain V-I region WOL Ig kappa chain V-II region MIL Ig kappa chain V-II region TEW Ig heavy chain V-I region Mot Ig heavy chain V-I region WOL Ig lambda chain V-I region NIG-64 Ig kappa chain V-III region HAH p-S19,S23-NFKBIB Ig lambda chain V-II region NIG-58 Ig heavy chain V-I region EU Ig kappa chain V-III region HAH Ig lambda chain V-VII region MOT ATPIg kappa chain V-I region HK101 Ig heavy chain V-III region HIL Ig kappa chain V-III region NG9 Ig kappa chain V-II region FR Ig heavy chain V-I region ND Ig lambda chain V-VI region SUT p-S157,S161-NFKBIE CALM1IGHV7-81Ig kappa chain V-I region BAN p-BCL10Ig kappa chain V-I region Kue Ig kappa chain V-I region Scw ATPIg heavy chain V-I region ND Ig heavy chain V-II region HE Ig heavy chain V-II region WAH Ig lambda chain V-V region DEL Ig kappa chain V region EV15 p-Y194,Y195,Y272-SHC1-1IGKCFe3+ Ig heavy chain V-I region SIE PIIg kappa chain V-III region VG IGLC6p21 RASGTPIg lambda chain V-II region BUR p-S559,S644,S652-CARD11p-T187-MAP3K7 PPIA Ig lambda chain V-II region TOG Ig heavy chain V-III region HIL Ig heavy chain V-III region WEA SH3KBP1 Ig lambda chain V-VI region WLT IGHDIg kappa chain V-I region HK101 IGKV4-1Ig kappa chain V-I region Walker SHC1 p46/p52Ig lambda chain V-II region NEI PIK3CD Ig kappa chain V-I region Bi Ig heavy chain V-III region POM Ig heavy chain V-III region TUR CD19 SignalosomeIP3 receptorIP3 complexIg kappa chain V-I region AG Ig heavy chain V-III region BUT Ig lambda chain V-V region DEL Ig kappa chain V-I region WAT Ig lambda chain V-IV region Kern Ig kappa chain V region EV15 Ig kappa chain V-III region GOL Ig kappa chain V-III region HAH IGLC7Ig kappa chain V-I region BAN Ig lambda chain V-II region WIN IGKV1-5IGKV1-5Ig kappa chain V-I region Ni Ig kappa chain V-I region HK101 IGHVActivated PKC betaPSMC5 PIK3CDPIK3R1Ig kappa chain V-IV region JI CRAC channelIg lambda chain V-II region MGC RELA Ig kappa chain V-I region Daudi Ig heavy chain V-III region HIL Ig lambda chain V-I region EPS Ig kappa chain V-I region Gal Ig lambda chain V-II region MGC IGKCFBXW11 Ig kappa chain V-I region OU Ig heavy chain V-II region HE Ig kappa chain V-IV region JI Ig lambda chain V region 4A Ig lambda chain V-I region VOR ADPCALM1 BCAP SignalosomeIg lambda chain V-III region SH PSMA1 Ig lambda chain V-IV region X p-Y188,Y199-CD79A Ig lambda chain V-II region TRO IgH heavy chain V-III region VH26 precursor Ig heavy chain V-III region WEA Ig lambda chain V-II region TRO p-13S-NFATC3 Ig lambda chain V-II region NIG-84 Ig kappa chain V-I region Mev Ig kappa chain V-III region POM SH3KBP1 Ig kappa chain V-III region B6 NF-kappaB p50/p65/c-Rel DimerIg lambda chain V-II region BOH IGHDMALT1Ig kappa chain V-I region DEE Ig heavy chain V-I region Mot Ig kappa chain V-IV region B17 Ig kappa chain V-I region Mev Ig heavy chain V-I region SIE Ig kappa chain V-II region MIL Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-III region BUT p-14S-NFATC2 RELA Ig lambda chain V-VI region SUT IGKV1-5CHUK PIK3R1 Ig lambda chain V-I region WAH Ig lambda chain V-I region EPS IGHV7-81Ig heavy chain V-III region WEA Ig heavy chain V-III region LAY Ig heavy chain V-III region TIL Ig kappa chain V-II region GM607 Tacrolimus Ig lambda chain V-VI region NIG-48 Ig kappa chain V-IV region B17 Ig heavy chain V-II region ARH-77 Ig lambda chain V-IV region Bau Ig lambda chain V-VI region EB4 Ig lambda chain V-II region VIL Ig lambda chain V-IV region MOL Ig kappa chain V-II region TEW Ig kappa chain V-III region CLL Ig kappa chain V-I region EU Ig kappa chain V-I region Bi Ig kappa chain V-I region Walker Ig lambda chain V-II region NEI Ig heavy chain V-III region TEI AntigenLYNPSMA5 Ig kappa chain V-I region HK101 Ig heavy chain V-III region TEI REL Ig kappa chain V-I region Kue Ig kappa chain V-I region Lay Ig heavy chain V-I region WOL Ig kappa chain V-II region Cum Ig lambda chain V-I region BL2 Ig heavy chain V-III region TRO Ig heavy chain V-III region WAS Ig kappa chain V-I region Ka Ig kappa chain V-III region VH Ig lambda chain V-I region HA Ig heavy chain V-III region POM Ig lambda chain V-II region NEI Ig heavy chain V-III region LAY RELA Ig lambda chain V-VII region MOT PSMB4 CD19VAV1Ig heavy chain V-II region ARH-77 RasGRP1/3Ig heavy chain V-I region EU Ig heavy chain V-III region WAS Ig kappa chain V-IV region JI Ig kappa chain V-I region Roy Ig kappa chain V-IV region STH Ig kappa chain V-III region VH Ig lambda chain V-IV region Kern PSMC6Ig kappa chain V-I region WEA Ig kappa chain V-II region TEW IGLVIg kappa chain V-I region Rei GRB2-1 Ig lambda chain V-II region MGC Dephosphorylated NFATC1/2/3IGLC7Ig lambda chain V-II region VIL Ig lambda chain V-I region VOR Ig lambda chain V-I region NIG-64 Ig lambda chain V-III region SH REL Ig kappa chain V-I region BAN Ig kappa chain V-I region Roy Ig kappa chain V-I region Mev Ig kappa chain V-III region WOL Ig kappa chain V-III region SIE p-BCL10 Ig heavy chain V-II region MCE IGLC6Ig heavy chain V-II region DAW Ig kappa chain V-I region Kue Ig kappa chain V-I region HK101 Ig lambda chain V-I region VOR Ig heavy chain V-III region JON Ig kappa chain V-I region DEE Ig lambda chain V-VI region SUT Ig lambda chain V-IV region Bau Ig lambda chain V-I region NEWM Ig lambda chain V-I region MEM Ig kappa chain V-III region WOL Ig kappa chain V-IV region Len p-4Y-PIK3AP1 UbIg kappa chain V-II region RPMI 6410 Ig kappa chain V region EV15 Ig lambda chain V-VII region MOT IGLC7Ig kappa chain V-II region GM607 Ig lambda chain V-I region WAH Ig kappa chain V-IV region JI Ig heavy chain V-III region TRO Ig kappa chain V-III region SIE PLC gamma1/2Ig lambda chain V region 4A IGLC1ITPR3 Ig lambda chain V-II region BUR IGLC6Ig lambda chain V-I region NEWM Ig heavy chain V-I region Mot PSMB5 Ig lambda chain V-II region VIL Ig lambda chain V-IV region Hil Ig kappa chain V-II region Cum Ig heavy chain V-II region NEWM Ig heavy chain V-III region BUR Ig kappa chain V region EV15 PSMA7Ig lambda chain V-VI region EB4 Ig lambda chain V-II region MGC Fe3+ IKKAIKKBNEMOIg lambda chain V-II region TRO p-S32,S36-NFKBIA Ig kappa chain V-I region Bi Ig kappa chain V-I region AG Ig kappa chain V-III region CLL Ig kappa chain V-III region POM Ig lambda chain V-I region HA Ig kappa chain V region EV15 Ig heavy chain V-II region DAW Ig heavy chain V-I region SIE Ig lambda chain V-II region TOG NRAS Ig heavy chain V-II region MCE Ig kappa chain V-I region AU Ig heavy chain V-III region CAM Ig heavy chain V-III region TRO Ig kappa chain V-I region Walker Ig lambda chain V-VI region AR BLNK PSMB2 PPP3CA IGKV1-5Ig heavy chain V-I region HG3 Ig heavy chain V-II region HE Ig kappa chain V-II region FR Ig lambda chain V-II region NEI CHUK Ig kappa chain V-III region SIE Ig kappa chain V-II region FR Ig kappa chain V-I region Roy Ig heavy chain V-I region SIE p-6Y-SYK Ig lambda chain V-VI region WLT PSMB10 Ig kappa chain V region EV15 IGHVGTP Ig heavy chain V-I region EU IGKVA18p-6Y-CD19 Ig heavy chain V-I region HG3 Ig kappa chain V-I region WEA Ig heavy chain V-III region JON BCRIg kappa chain V-I region WAT IGHMIg kappa chain V-II region TEW Ig heavy chain V-III region WAS Ig kappa chain V-I region AG Ig lambda chain V-II region MGC PSMD1 Ig kappa chain V-I region Walker Ig lambda chain V-II region TRO Ig lambda chain V-I region WAH Ig kappa chain V-I region Rei Ig kappa chain V-I region Daudi NF-kappaBp-IkBSCF-betaTrCPIg heavy chain V-III region BRO Ig lambda chain V-III region LOI Ig heavy chain V-I region HG3 Ig lambda chain V-VI region AR Ig kappa chain V-III region WOL Ig heavy chain V-II region OU CARMA1 oligomerIg kappa chain V-I region AU Ig kappa chain V-I region Gal Ig kappa chain V-IV region STH IGLC1Ig lambda chain V-IV region Bau IGKVA18Ig kappa chain V-I region Ka NFKBIB Ig heavy chain V-III region TEI Ig lambda chain V-I region HA IGLC7Ig heavy chain V-III region BUR PSMD10 STIM1 Active IKK complexIg kappa chain V-I region Mev Ig kappa chain V-I region Kue Ig kappa chain V-II region RPMI 6410 Ig kappa chain V-I region AU Ig kappa chain V-III region B6 Ig kappa chain V-I region Ka Ig heavy chain V-III region TEI Ig lambda chain V-VI region WLT FKBP1ATacrolimusIg kappa chain V-I region AU Ig lambda chain V-III region LOI VAV1 Ig lambda chain V-III region SH Ig lambda chain V-I region NEW PSMB8 Ig lambda chain V-II region TOG Ig heavy chain V-I region SIE Ig lambda chain V-III region SH Ig kappa chain V-III region IARC/BL41 Ig heavy chain V-II region NEWM IGHMIg lambda chain V-II region TRO Orai1 dimerIg heavy chain V-III region TIL SKP1 Ig kappa chain V-III region IARC/BL41 PSMA4 Ig kappa chain V-III region HIC Ig kappa chain V-II region GM607 Ig lambda chain V-II region NIG-84 PSMD3 Ig kappa chain V-III region SIE Ig lambda chain V-II region BO Ig heavy chain V-III region POM Ig heavy chain V-II region NEWM Ig lambda chain V-II region TRO Ig kappa chain V-I region Roy Ig heavy chain V-III region GA PIK3R1 IGLC1Ig lambda chain V-VII region MOT p-S157,S161-NFKBIE Ig heavy chain V-I region Mot FYNATPIg heavy chain V-II region COR Ig kappa chain V-III region Ti IGLVBTRC Ig lambda chain V-II region TRO IKBKG Ig kappa chain V-III region GOL IGKCIg kappa chain V-I region Scw Ig lambda chain V-II region WIN Ig lambda chain V-V region DEL Ig heavy chain V-II region COR PIIg kappa chain V-II region MIL Ig kappa chain V-II region FR Ig kappa chain V-I region Hau GRB2-1 Ig heavy chain V-II region DAW Ig lambda chain V-I region EPS Ig kappa chain V-I region Lay RELA GRB2-1 PSMD6CARMA1BCL10MALT1TAK1Ig lambda chain V-I region NEWM HRASIg heavy chain V-II region DAW PPP3CA Ig heavy chain V-I region EU Ig heavy chain V-III region TUR Ig lambda chain V-II region BO Ig kappa chain V-III region CLL STIM1 Ig lambda chain V-I region BL2 Ig heavy chain V-I region HG3 Ig heavy chain V-III region ZAP NFKB1Ig lambda chain V-VI region WLT Ig kappa chain V-I region WAT CBL Ig heavy chain V-III region HIL IGHV7-81Ig kappa chain V-II region FR Ig kappa chain V-III region CLL Ig lambda chain V-II region TOG Ig kappa chain V-IV region STH Ig heavy chain V-III region WEA Ig kappa chain V-III region NG9 Ig heavy chain V-III region WAS Ig heavy chain V-III region BRO Ig kappa chain V-III region GOL Ig kappa chain V-IV region STH RELA PSME3 Ig kappa chain V-III region POM Ig kappa chain V-III region CLL Ig lambda chain V region 4A Ig lambda chain V-IV region Hil NFKB1IgH heavy chain V-III region VH26 precursor ATPp-Y188,Y199-CD79A Ig kappa chain V-II region Cum Ig heavy chain V-III region BUR NF-kappa-B p50/ p65/c-Relp-IKBISOS1 BLNKGRB2SOS1CIN85CBLIg heavy chain V-II region OU Ig heavy chain V-I region Mot Ig lambda chain V-IV region Kern IGLVIg lambda chain V region 4A p-Y753,Y759,Y1217-PLCG2 Ig lambda chain V-IV region Hil KRASIg lambda chain V-VI region SUT Ig kappa chain V-III region VH Ig heavy chain V-II region WAH Ig lambda chain V-IV region Hil Ig lambda chain V-VII region MOT IGLVIg lambda chain V-I region BL2 Ig heavy chain V-II region MCE Ig kappa chain V-I region EU Ig lambda chain V-II region BOH Ig lambda chain V-III region LOI CD19 Ig heavy chain V-I region ND AntigenBCRCa2+ Ig heavy chain V-II region DAW IGLC3Ig kappa chain V-I region Hau p-BCL10 Ig heavy chain V-III region TUR p-Y139-DAPP1 IGLC1Ig kappa chain V-III region Ti PSMB11 CD79A Ig kappa chain V-III region GOL Ig kappa chain V-I region BAN Ig kappa chain V-I region Walker Ig heavy chain V-II region ARH-77 Ig heavy chain V-III region DOB CALM1 IGKVA18Ig heavy chain V-II region MCE GRB2-1 Ca2+ Ig lambda chain V-I region MEM IGKV4-1Antigenp-BCRp-SYKp-BLNKVAV1 SH3KBP1 Ig kappa chain V-IV region Len Ig kappa chain V-I region Roy Ig heavy chain V-II region HE Ig kappa chain V-I region WEA PSMC1IGKVA18Ig heavy chain V-III region DOB PSMB9 Ig lambda chain V-VI region SUT PSMD4Ig kappa chain V-I region Daudi PSMB7 p-S559,S644,S652-CARD11Ig kappa chain V-I region Ni ATPIg kappa chain V-I region WAT Ig heavy chain V-III region CAM Antigenp-BCRp-SYKp-Y196,Y207-CD79B Ig heavy chain V-III region BUT Ig kappa chain V region EV15 Ig lambda chain V-II region VIL IIg kappa chain V-I region Ni Ig lambda chain V-VI region NIG-48 IGLC2Ig lambda chain V-I region VOR Ig lambda chain V-I region EPS Ig lambda chain V-III region LOI Ig heavy chain V-III region TIL Ig kappa chain V-I region CAR Ig heavy chain V-III region JON CUL1 Ig heavy chain V-III region DOB Ig heavy chain V-II region WAH Ig kappa chain V-I region Ni IGLC3Ig heavy chain V-II region SESS Ig heavy chain V-III region BRO Ig heavy chain V-II region ARH-77 Ig kappa chain V-III region GOL Ig kappa chain V-II region MIL Ig kappa chain V-I region Lay CalcineurinPhosphorylated NFATC1/2/3Ig kappa chain V-I region OU Ig heavy chain V-III region POM Ig kappa chain V-I region Bi Ig heavy chain V-II region OU FBXW11 Ig heavy chain V-II region NEWM Ig lambda chain V-III region LOI Ig lambda chain V-II region NIG-84 CBLB Ig lambda chain V-II region NIG-58 PPP3CBIg kappa chain V-III region Ti Ig lambda chain V-VI region NIG-48 Ig heavy chain V-III region ZAP Ig heavy chain V-III region GAL Ig kappa chain V-III region HIC Ig lambda chain V-I region WAH IGLC6PIK3CDPIK3R1Ig heavy chain V-III region BUR PIK3AP1Ig heavy chain V-II region ARH-77 STIM1 p-S559,S644,S652-CARD11Ig lambda chain V-I region HA Ig kappa chain V-I region Scw Ig kappa chain V-III region HIC Ig kappa chain V-I region CAR Ig kappa chain V-I region Walker Ig lambda chain V-I region MEM NFKB1Ig kappa chain V-I region DEE IGKVA18p21 RASGDPIg heavy chain V-II region NEWM p-Y188,Y199-CD79A Ig lambda chain V-II region VIL NFKBIE Ig kappa chain V-I region Bi Ig lambda chain V-I region EPS PSMA2 Ig kappa chain V-I region Rei NRAS Ig lambda chain V-II region BOH Ig kappa chain V-I region OU Ig kappa chain V-II region GM607 Ig heavy chain V-III region TUR IKBKG Ig kappa chain V-I region Gal CD79B SYKIg kappa chain V-I region BAN PSMD5 Ig kappa chain V-I region Wes Ig lambda chain V-II region NIG-58 Ig heavy chain V-III region TUR REL ORAI1 Ig heavy chain V-III region NIE Ig kappa chain V-I region AU Ig heavy chain V-III region CAM Ig lambda chain V-I region MEM SCF-beta-TrCp1/2Ca2+Ig lambda chain V-I region NIG-64 PSMD11 p-Y196,Y207-CD79B Ig lambda chain V-VI region NIG-48 Ig heavy chain V-III region BUR PSMC4 p-5Y-BLNK ITPR2 Ig lambda chain V-IV region X Ig heavy chain V-III region TIL PIK3CD Ig kappa chain V-I region Hau HRASIg kappa chain V-I region WEA GDP IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Daudi Ig lambda chain V-VI region NIG-48 Ig heavy chain V-III region GAL IGKCp-Y196,Y207-CD79B CARD11p-Y196,Y207-CD79B Ig lambda chain V-II region TOG Ig lambda chain V-IV region X Ig kappa chain V-I region BAN Ig kappa chain V-I region Scw Ig heavy chain V-III region BRO ADPIg kappa chain V-I region Mev Ig kappa chain V-IV region B17 IGHV7-81Ig heavy chain V-I region ND Ig kappa chain V-II region FR REL Ig kappa chain V-IV region Len Ig kappa chain V-I region WEA Ig lambda chain V-II region WIN IGLC1ADPIg kappa chain V-III region HAH Ig kappa chain V-I region Lay Ig kappa chain V-II region Cum Ig lambda chain V-II region NIG-84 DAG Ig kappa chain V-I region Rei MAP3K7Ig heavy chain V-II region MCE p-RasGRP1,3DAGIg kappa chain V-III region NG9 Ig kappa chain V-I region OU Ig kappa chain V-III region GOL Ig heavy chain V-III region TUR IGLC1Ig heavy chain V-III region DOB IGHVNCK1Ig kappa chain V-I region EU NFKB1Ig lambda chain V-IV region Kern Ig lambda chain V-V region DEL Ig kappa chain V-I region Ni Ig heavy chain V-I region EU Ig kappa chain V-III region POM Ig heavy chain V-II region NEWM Antigenp-BCRSYKIg heavy chain V-III region POM Ig lambda chain V-II region BUR Ig lambda chain V-I region NEW Ig kappa chain V-I region Hau IGLC6Ig heavy chain V-III region TRO Ig kappa chain V-I region Mev Ig lambda chain V-I region BL2 Ig heavy chain V-III region LAY Ig heavy chain V-III region CAM IGHDSOS1 Ig kappa chain V-II region MIL Ig kappa chain V-I region OU Ig kappa chain V-II region TEW Ig lambda chain V-II region NIG-58 Ig kappa chain V-IV region JI IGLC3IGHMSYK Ig heavy chain V-I region WOL Ig kappa chain V-III region VG Ig lambda chain V-IV region MOL Ig heavy chain V-III region WAS ATPIg lambda chain V-IV region MOL PIIg heavy chain V-III region GA VAV1 Ig kappa chain V-I region BAN Ig kappa chain V-I region Kue IGHDIg lambda chain V-II region BO Ig kappa chain V-II region Cum Ig lambda chain V-VI region AR Ig kappa chain V-I region WEA Ig heavy chain V-III region DOB Ig kappa chain V-I region Ka Ig kappa chain V-I region AG Ig kappa chain V-III region POM Ig lambda chain V-IV region Hil ITPR3 Ig heavy chain V-II region NEWM Ig heavy chain V-III region DOB NF-kappaB p50/p65/c-Relub-p-IKBIg kappa chain V-I region Scw REL DAG Ig kappa chain V-I region Ni Ig heavy chain V-III region BUT Ig lambda chain V-I region HA Ig kappa chain V-III region POM Ig kappa chain V-III region IARC/BL41 Ig lambda chain V-II region BUR CBL Ig heavy chain V-III region TEI Ig kappa chain V-III region WOL Ig heavy chain V-III region NIE Ig heavy chain V-I region EU Ig lambda chain V-II region NEI IGKV4-1Ig lambda chain V-II region VIL PSMD9 Zn2+ Ig heavy chain V-III region TIL PSMD7Ig heavy chain V-III region ZAP Ig lambda chain V-IV region Bau Ca2+PRKCBIg lambda chain V-VI region AR Ig heavy chain V-III region LAY Ig kappa chain V-I region CAR Ig lambda chain V-I region WAH Ig heavy chain V-III region LAY Phosphatidylserinep-12S-NFATC1 Ig kappa chain V-III region NG9 Ca2+PSMD8 BTKIg kappa chain V-I region Wes Ig heavy chain V-III region HIL Ig lambda chain V-VI region WLT Ig kappa chain V-IV region STH Ig heavy chain V-II region COR Ig kappa chain V-I region Gal p-6Y-SYK IGLC6PRKCB Ig lambda chain V-I region EPS Ig kappa chain V-III region SIE ITPR2 p-T133-RASGRP3 p-Y188,Y199-CD79A Ig kappa chain V-I region Wes Ig heavy chain V-III region WAS VAV1Ig kappa chain V-I region WEA Ig heavy chain V-III region KOL Ig lambda chain V-II region BOH Ig kappa chain V-I region Daudi IGHV7-81Ig kappa chain V-I region Hau Ig heavy chain V-III region JON Ig heavy chain V-III region GA Ig lambda chain V-V region DEL Ig heavy chain V-III region CAM Ig heavy chain V-III region TRO Ig kappa chain V-III region WOL Ig lambda chain V-III region LOI IGHVIg lambda chain V-I region MEM ITPR1 Ig lambda chain V-IV region Hil Ig lambda chain V-I region MEM Ig kappa chain V-III region NG9 IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region CAR Ig kappa chain V-III region B6 PSMC2 p-6Y-SYK Ig kappa chain V-I region Wes Cyclophilin ACyclosporin AIg kappa chain V-I region HK101 Ig kappa chain V-IV region Len Ig kappa chain V-I region CAR Ig lambda chain V-IV region Kern Ig heavy chain V-III region TUR Ig kappa chain V-I region OU Ig kappa chain V-I region Scw Ig kappa chain V-I region EU STIM1TRPC1PSMB3 Ig heavy chain V-I region SIE Ig heavy chain V-II region DAW IGHMIg lambda chain V region 4A Ig heavy chain V-III region NIE Ig heavy chain V-III region TEI Ig kappa chain V-III region HAH Ig heavy chain V-III region NIE Ig kappa chain V-I region DEE IGLC3Ig heavy chain V-II region COR Ig kappa chain V-I region DEE p-S19,S23-NFKBIB Ig kappa chain V-III region HAH Ig kappa chain V-II region FR Ig heavy chain V-II region OU Ig heavy chain V-II region SESS Ig heavy chain V-III region TEI CBL MALT1 Ig lambda chain V-IV region Kern Ig lambda chain V-I region NEW Ig lambda chain V region 4A Ig kappa chain V-II region GM607 Ig lambda chain V-II region WIN CHUK Ig heavy chain V-III region GA Ig lambda chain V-II region NEI IGLVIg lambda chain V-II region WIN Ig kappa chain V-I region Rei Ig kappa chain V-I region Kue Ig lambda chain V-VI region AR p-Y188,Y199-CD79A NFKB1Ig kappa chain V-I region Walker Ig lambda chain V-II region NEI Antigenp-BCRIg lambda chain V-IV region Hil Ig kappa chain V-III region B6 Ig kappa chain V-I region AG p-Y239,Y240,Y317-SHC1-2 NF-kappaB p50/p65/c-Rel DimerIg heavy chain V-III region GAL Ig heavy chain V-I region SIE CUL1 TRPC1Ig kappa chain V-I region Mev Ig lambda chain V-VI region EB4 IgH heavy chain V-III region VH26 precursor Ig heavy chain V-III region BUR Ig kappa chain V-III region VH Ig lambda chain V-II region MGC p-5Y-BLNK Ig kappa chain V-IV region Len STIM1CalciumIg lambda chain V-VI region EB4 Ig heavy chain V-II region SESS IGHVZn2+ IGLC3Ig heavy chain V-I region Mot Calcineurin ORAI1 p-S32,S36-NFKBIA IGKV4-1Ig kappa chain V-I region AU NCK1 BTRC Ig kappa chain V-I region Rei MALT1 Ig heavy chain V-III region GA PIP3 activates AKT signalingIGKV4-1Ig kappa chain V-I region WAT Ig heavy chain V-III region KOL IGLC2PIKRASPSMC3 Ig heavy chain V-I region WOL IGHDIg kappa chain V-III region B6 Ig kappa chain V-I region Roy Ig lambda chain V-IV region X Ig heavy chain V-III region GA Ig kappa chain V-IV region B17 Ig lambda chain V-I region NIG-64 Ig kappa chain V-III region SIE Ig kappa chain V-I region Gal Ig kappa chain V-I region Daudi Ig heavy chain V-II region WAH Ig heavy chain V-I region WOL Ig heavy chain V-III region ZAP Ig heavy chain V-III region BUT IGKV1-5Ig lambda chain V-II region NIG-84 Ig kappa chain V-III region POM Ig kappa chain V-I region Scw Ig lambda chain V-I region BL2 Ig lambda chain V-I region VOR Ig kappa chain V-I region AU PSMF1Ig kappa chain V-I region Wes Ig heavy chain V-III region NIE IGLC2Ig kappa chain V-I region Gal Ig lambda chain V-I region BL2 Ig lambda chain V-VI region SUT IGLC2Ig kappa chain V-I region AG Ig kappa chain V-II region TEW MALT1 CD79B IGHMPhosphorylated NFATC1/2/3SKP1 Ig kappa chain V-III region Ti IGHMIg kappa chain V-III region WOL Ig heavy chain V-III region BUT Ig kappa chain V-III region SIE Ig kappa chain V-III region VG Ig kappa chain V-IV region B17 PSME2 PSMD12 Ig kappa chain V-I region OU Ig kappa chain V-II region RPMI 6410 PIK3CD Ig lambda chain V-VI region SUT PSMB1 Ig lambda chain V-IV region X Ig lambda chain V-I region NEW Ig kappa chain V-III region VG DAGIGKV4-1Ig lambda chain V-IV region MOL Ig heavy chain V-III region ZAP FKBP1A Ig lambda chain V-VII region MOT ITPR1 Ig kappa chain V-IV region STH Ig heavy chain V-III region HIL Ig lambda chain V-II region BUR Ig kappa chain V-IV region B17 Ig heavy chain V-II region OU STIM1 DimerIGLVIg lambda chain V-II region BO Ig kappa chain V-III region Ti Ig lambda chain V-I region NEW IGLC7PPP3CBp-S177,S181-IKBKB Ig heavy chain V-II region DAW Ig heavy chain V-III region WEA Ig lambda chain V-VI region WLT PSMA8 Ig heavy chain V-I region ND Ig heavy chain V-III region HIL Ig heavy chain V-III region TIL Ig lambda chain V-II region NIG-84 IGHDIg heavy chain V-III region NIE Ig lambda chain V-I region NEW Ig lambda chain V-II region TOG Ig kappa chain V-I region EU Ig kappa chain V-III region GOL Ig lambda chain V-II region TOG IGHV7-81SOS1 Ig kappa chain V-II region RPMI 6410 Ig lambda chain V region 4A Ig lambda chain V-II region WIN IGKV4-1Ig lambda chain V-VI region NIG-48 p-BCL10 CARMA1MALT1BCL10Ig lambda chain V-II region BO Ig lambda chain V-II region BOH Ig kappa chain V-IV region Len PSME1 IGLC2Ig lambda chain V-VI region EB4 Ig kappa chain V-I region Kue Ig lambda chain V-I region NIG-64 IGKVA18Ig heavy chain V-II region COR Ig kappa chain V-II region Cum Ig kappa chain V-I region Rei Ig lambda chain V-I region VOR CARMA1BCL10MALT1TAK1IKKIg kappa chain V-III region Ti Ig heavy chain V-III region GAL IGLC2Ig kappa chain V-III region IARC/BL41 Ig kappa chain V-I region Roy IGHV7-81Ig heavy chain V-III region DOB IGLC1Ig lambda chain V-VI region AR Ig lambda chain V-I region VOR Ig lambda chain V-I region HA Ig kappa chain V-III region B6 Ig kappa chain V-I region AG Ig lambda chain V-IV region Bau Ig kappa chain V-I region CAR Ig kappa chain V-II region MIL Ig kappa chain V-III region VH PSME4 IKBKB Ca2+ Ig lambda chain V-II region NIG-58 IGKVA18Ig heavy chain V-III region POM Ig lambda chain V-III region SH Ca2+ Ig kappa chain V-III region IARC/BL41 Ig heavy chain V-III region KOL Ig heavy chain V-III region LAY p-S19,S23-Ub-NFKBIB PSMD14 Ig lambda chain V-II region BOH Ig lambda chain V-I region NEWM ADPIg kappa chain V-III region CLL IGHVIg heavy chain V-III region BRO Ig kappa chain V-I region Wes Ig lambda chain V-I region HA Ig lambda chain V-II region BOH Ig heavy chain V-II region HE Ig kappa chain V-I region Hau Ig kappa chain V-III region VG Ig kappa chain V-IV region JI IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Ka Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-VI region EB4 Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-I region NIG-64 Ig kappa chain V-III region CLL Ig lambda chain V-IV region Bau Ig kappa chain V-II region MIL Ig lambda chain V-III region SH PIIGLC6Phosphatidylserine Ig kappa chain V-I region Bi Ig kappa chain V-II region GM607 Ig kappa chain V-I region Gal Ig lambda chain V-I region WAH Ig heavy chain V-III region WAS Ig lambda chain V-II region BUR Ig kappa chain V-I region HK101 Ig kappa chain V-III region HAH Ig lambda chain V-I region NEWM Ig kappa chain V-I region DEE Ig lambda chain V-I region NEWM Ig lambda chain V-VII region MOT Ig heavy chain V-II region WAH PPP3R1 IGKV1-5Ig heavy chain V-III region JON CD79A Ig heavy chain V-III region KOL Ig heavy chain V-II region MCE IP3 receptor homotetramerIg kappa chain V-II region TEW Ig heavy chain V-I region Mot Ig lambda chain V-II region NIG-58 Ig kappa chain V-I region EU Ig kappa chain V-III region VG Ig lambda chain V-II region VIL Ig heavy chain V-III region TRO Ig heavy chain V-III region GAL Ig heavy chain V-II region HE PIK3R1 IGLC7Ig heavy chain V-III region WEA Ig heavy chain V-III region KOL IGLC3Ig kappa chain V-I region Ka Ig kappa chain V-III region IARC/BL41 IGKCIg kappa chain V-II region GM607 STIM1 PSMD2 IgH heavy chain V-III region VH26 precursor Ig heavy chain V-I region ND NFKBIA Ig heavy chain V-II region OU Ig lambda chain V-I region BL2 Ig kappa chain V-IV region STH Ig lambda chain V-I region NEW Ig kappa chain V-III region B6 Ig kappa chain V-I region Daudi Ig lambda chain V-IV region MOL Ig kappa chain V-I region Lay Ig kappa chain V-III region WOL p-T187-MAP3K7 7779, 115, 131, 14111, 10428, 1302, 86, 92, 991414012729, 1142916312314333, 37, 14379, 91, 115, 123, 1413227, 31, 72, 139148608125123


Description

Mature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel et al. 1975, Van Noesel et al. 1992, Sanchez et al. 1993, reviewed in Brezski and Monroe 2008). Binding of antigen to the immunoglobulin activates phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of Ig-alpha and Ig-beta by Src family tyrosine kinases, including LYN, FYN, and BLK (Nel et al. 1984, Yamanashi et al. 1991, Flaswinkel and Reth 1994, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Gauld and Cambier 2004, reviewed in Harwood and Batista 2010).
The protein kinase SYK binds the phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on the cytoplasmic tails of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Wienands et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding causes the activation and autophosphorylation of SYK (Law et al. 1994, Baldock et al. 2000, Irish et al. 2006, Tsang et al. 2008, reviewed in Bradshaw 2010).
Activated SYK and other kinases phosphorylate BLNK (SLP-65), BCAP, and CD19 which serve as scaffolds for the assembly of large complexes, the signalosomes, by recruiting phosphoinositol 3-kinase (PI3K), phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.
PLC-gamma associated with BLNK hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (Carter et al. 1991, Kim et al. 2004). IP3 binds receptors on the endoplasmic reticulum and causes release of calcium ions from the ER into the cytosol. The depletion of calcium from the ER in turn activates STIM1 to interact with ORAI and TRPC1 channels in the plasma membrane, resulting in an influx of extracellular calcium ions (Muik et al. 2008, Luik et al. 2008, Park et al. 2009, Mori et al. 2002). PI3K associated with BCAP and CD19 phosphorylates phosphatidylinositol 4,5-bisphosphate to yield phosphatidyinositol 3,4,5-trisphosphate.
Second messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidylinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RAS is activated via RasGRP proteins, NF-AT is activated via calcineurin, and AKT (PKB) is activated via PDK1 (reviewed in Shinohara and Kurosaki 2009, Stone 2006). Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=983705

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  52. Aiba Y, Kameyama M, Yamazaki T, Tedder TF, Kurosaki T.; ''Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase.''; PubMed Europe PMC Scholia
  53. Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F, Ben-Neriah Y.; ''Identification of the receptor component of the IkappaBalpha-ubiquitin ligase.''; PubMed Europe PMC Scholia
  54. Fuchs SY, Chen A, Xiong Y, Pan ZQ, Ronai Z.; ''HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin.''; PubMed Europe PMC Scholia
  55. Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF.; ''NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways.''; PubMed Europe PMC Scholia
  56. Baba Y, Hashimoto S, Matsushita M, Watanabe D, Kishimoto T, Kurosaki T, Tsukada S.; ''BLNK mediates Syk-dependent Btk activation.''; PubMed Europe PMC Scholia
  57. Harwood NE, Batista FD.; ''Early events in B cell activation.''; PubMed Europe PMC Scholia
  58. Carter RH, Park DJ, Rhee SG, Fearon DT.; ''Tyrosine phosphorylation of phospholipase C induced by membrane immunoglobulin in B lymphocytes.''; PubMed Europe PMC Scholia
  59. Flaswinkel H, Reth M.; ''Dual role of the tyrosine activation motif of the Ig-alpha protein during signal transduction via the B cell antigen receptor.''; PubMed Europe PMC Scholia
  60. Ghosh CC, Vu HY, Mujo T, Vancurova I.; ''Analysis of nucleocytoplasmic shuttling of NF kappa B proteins in human leukocytes.''; PubMed Europe PMC Scholia
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  63. Nishizumi H, Horikawa K, Mlinaric-Rascan I, Yamamoto T.; ''A double-edged kinase Lyn: a positive and negative regulator for antigen receptor-mediated signals.''; PubMed Europe PMC Scholia
  64. Whiteside ST, Epinat JC, Rice NR, Israël A.; ''I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity.''; PubMed Europe PMC Scholia
  65. Loh C, Shaw KT, Carew J, Viola JP, Luo C, Perrino BA, Rao A.; ''Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity.''; PubMed Europe PMC Scholia
  66. Marshall AJ, Niiro H, Lerner CG, Yun TJ, Thomas S, Disteche CM, Clark EA.; ''A novel B lymphocyte-associated adaptor protein, Bam32, regulates antigen receptor signaling downstream of phosphatidylinositol 3-kinase.''; PubMed Europe PMC Scholia
  67. Baeuerle PA, Baltimore D.; ''Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.''; PubMed Europe PMC Scholia
  68. Batiuk TD, Kung L, Halloran PF.; ''Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.''; PubMed Europe PMC Scholia
  69. Chen L, Monti S, Juszczynski P, Daley J, Chen W, Witzig TE, Habermann TM, Kutok JL, Shipp MA.; ''SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma.''; PubMed Europe PMC Scholia
  70. Fagerlund R, Melén K, Cao X, Julkunen I.; ''NF-kappaB p52, RelB and c-Rel are transported into the nucleus via a subset of importin alpha molecules.''; PubMed Europe PMC Scholia
  71. Ohba Y, Mochizuki N, Yamashita S, Chan AM, Schrader JW, Hattori S, Nagashima K, Matsuda M.; ''Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3.''; PubMed Europe PMC Scholia
  72. 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
  73. Alicia S, Angélica Z, Carlos S, Alfonso S, Vaca L.; ''STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: moving TRPC1 in and out of lipid rafts.''; PubMed Europe PMC Scholia
  74. Hata D, Nakamura T, Kawakami T, Kawakami Y, Herren B, Mayumi M.; ''Tyrosine phosphorylation of MB-1, B29, and HS1 proteins in human B cells following receptor crosslinking.''; PubMed Europe PMC Scholia
  75. Wesselborg S, Fruman DA, Sagoo JK, Bierer BE, Burakoff SJ.; ''Identification of a physical interaction between calcineurin and nuclear factor of activated T cells (NFATp).''; PubMed Europe PMC Scholia
  76. Matsuda M, Paterson HF, Rodriguez R, Fensome AC, Ellis MV, Swann K, Katan M.; ''Real time fluorescence imaging of PLC gamma translocation and its interaction with the epidermal growth factor receptor.''; PubMed Europe PMC Scholia
  77. Beals CR, Clipstone NA, Ho SN, Crabtree GR.; ''Nuclear localization of NF-ATc by a calcineurin-dependent, cyclosporin-sensitive intramolecular interaction.''; PubMed Europe PMC Scholia
  78. Buhl AM, Pleiman CM, Rickert RC, Cambier JC.; ''Qualitative regulation of B cell antigen receptor signaling by CD19: selective requirement for PI3-kinase activation, inositol-1,4,5-trisphosphate production and Ca2+ mobilization.''; PubMed Europe PMC Scholia
  79. Park CY, Hoover PJ, Mullins FM, Bachhawat P, Covington ED, Raunser S, Walz T, Garcia KC, Dolmetsch RE, Lewis RS.; ''STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.''; PubMed Europe PMC Scholia
  80. Shibasaki F, Price ER, Milan D, McKeon F.; ''Role of kinases and the phosphatase calcineurin in the nuclear shuttling of transcription factor NF-AT4.''; PubMed Europe PMC Scholia
  81. Weng WK, Jarvis L, LeBien TW.; ''Signaling through CD19 activates Vav/mitogen-activated protein kinase pathway and induces formation of a CD19/Vav/phosphatidylinositol 3-kinase complex in human B cell precursors.''; PubMed Europe PMC Scholia
  82. Irish JM, Czerwinski DK, Nolan GP, Levy R.; ''Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry.''; PubMed Europe PMC Scholia
  83. Li CC, Dai RM, Longo DL.; ''Inactivation of NF-kappa B inhibitor I kappa B alpha: ubiquitin-dependent proteolysis and its degradation product.''; PubMed Europe PMC Scholia
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  85. 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
  86. Papp E, Tse JK, Ho H, Wang S, Shaw D, Lee S, Barnett J, Swinney DC, Bradshaw JM.; ''Steady state kinetics of spleen tyrosine kinase investigated by a real time fluorescence assay.''; PubMed Europe PMC Scholia
  87. Valentine MA, Bursten SL, Harris WE, Draves KE, Pollok BA, Ostrowski J, Bomsztyk K, Clark EA.; ''Generation of phosphatidic acid and diacylglycerols following ligation of surface immunoglobulin in human B lymphocytes: potential role in PKC activation.''; PubMed Europe PMC Scholia
  88. Cheng KT, Liu X, Ong HL, Swaim W, Ambudkar IS.; ''Local Ca²+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca²+ signals required for specific cell functions.''; PubMed Europe PMC Scholia
  89. Kochs G, Hummel R, Fiebich B, Sarre TF, Marmé D, Hug H.; ''Activation of purified human protein kinase C alpha and beta I isoenzymes in vitro by Ca2+, phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate.''; PubMed Europe PMC Scholia
  90. Park J, Yaseen NR, Hogan PG, Rao A, Sharma S.; ''Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells.''; PubMed Europe PMC Scholia
  91. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  92. Law CL, Aruffo A, Chandran KA, Doty RT, Clark EA.; ''Ig domains 1 and 2 of murine CD22 constitute the ligand-binding domain and bind multiple sialylated ligands expressed on B and T cells.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
112687view16:08, 9 October 2020ReactomeTeamReactome version 73
101604view11:47, 1 November 2018ReactomeTeamreactome version 66
101140view21:32, 31 October 2018ReactomeTeamreactome version 65
100668view20:06, 31 October 2018ReactomeTeamreactome version 64
100218view16:51, 31 October 2018ReactomeTeamreactome version 63
99769view15:17, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93934view13:46, 16 August 2017ReactomeTeamreactome version 61
93521view11:25, 9 August 2017ReactomeTeamreactome version 61
87188view08:07, 19 July 2016EgonwOntology Term : 'signaling pathway' added !
86619view09:22, 11 July 2016ReactomeTeamreactome version 56
83158view10:13, 18 November 2015ReactomeTeamVersion54
81511view13:03, 21 August 2015ReactomeTeamVersion53
76984view08:27, 17 July 2014ReactomeTeamFixed remaining interactions
76689view12:05, 16 July 2014ReactomeTeamFixed remaining interactions
76015view10:07, 11 June 2014ReactomeTeamRe-fixing comment source
75724view11:19, 10 June 2014ReactomeTeamReactome 48 Update
75074view14:02, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74860view17:46, 2 May 2014EgonwMarked two metabolites as a DataNode type="Metabolite"...
74721view08:48, 30 April 2014ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexREACT_2353 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Activated PKC betaComplexREACT_4856 (Reactome)
Active CalmodulinComplexREACT_3178 (Reactome)
Active IKK complexComplexREACT_119869 (Reactome)
Antigen BCRComplexREACT_119368 (Reactome)
Antigen

p-BCR

SYK		ComplexREACT_120132 (Reactome)
Antigen

p-BCR p-SYK

p-BLNK		ComplexREACT_120231 (Reactome)
Antigen

p-BCR

p-SYK		ComplexREACT_120006 (Reactome)
Antigen p-BCRComplexREACT_119697 (Reactome)
AntigenREACT_119525 (Reactome)
BCAP SignalosomeComplexREACT_119322 (Reactome)
BCRComplexREACT_119956 (Reactome)
BLKProteinP51451 (Uniprot-TrEMBL)
BLNK

GRB2 SOS1 CIN85

CBL		ComplexREACT_120158 (Reactome)
BLNK ProteinQ8WV28 (Uniprot-TrEMBL)
BLNK ComplexREACT_120226 (Reactome)
BTKProteinQ06187 (Uniprot-TrEMBL)
BTRC ProteinQ9Y297 (Uniprot-TrEMBL)
CALM1 ProteinP62158 (Uniprot-TrEMBL)
CALM1ProteinP62158 (Uniprot-TrEMBL)
CARD11ProteinQ9BXL7 (Uniprot-TrEMBL)
CARMA1

BCL10 MALT1 TAK1

IKK		ComplexREACT_118993 (Reactome) TAK1 and the IKK complex are observed to migrate to lipid rafts containing phosphorylated CARMA1, BCL10, and MALT1. By analogy with NF-kappaB signaling pathways in other cells, the CARMA1:BCL10MALT1:TAK1:IKK complex in B cells may also contain TAB1, TAB2 and/or TAB3, TRAF6.
CARMA1

BCL10 MALT1

TAK1		ComplexREACT_119896 (Reactome) TAK1 and the IKK complex are observed to migrate to lipid rafts containing phosphorylated CARMA1, BCL10, and MALT1. By analogy with NF-kappaB signaling pathways in other cells, the CARMA1:BCL10MALT1:TAK1:IKK complex in B cells may also contain TAB1, TAB2 and/or TAB3, TRAF6.
CARMA1

MALT1

BCL10		ComplexREACT_119308 (Reactome)
CARMA1 oligomerComplexREACT_119167 (Reactome)
CBL ProteinP22681 (Uniprot-TrEMBL)
CBLB ProteinQ13191 (Uniprot-TrEMBL)
CD19 VAV1ComplexREACT_119973 (Reactome)
CD19 ProteinP15391 (Uniprot-TrEMBL)
CD19 SignalosomeComplexREACT_119603 (Reactome)
CD79A ProteinP11912 (Uniprot-TrEMBL)
CD79B ProteinP40259 (Uniprot-TrEMBL)
CHUK ProteinO15111 (Uniprot-TrEMBL)
CRAC channelComplexREACT_24443 (Reactome)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calcineurin Phosphorylated NFATC1/2/3ComplexREACT_119836 (Reactome)
Calcineurin ComplexREACT_119672 (Reactome)
Cyclophilin A Cyclosporin AComplexREACT_119713 (Reactome)
Cyclosporin A MetaboliteCHEBI:4031 (ChEBI)
DAG MetaboliteCHEBI:17815 (ChEBI)
DAGCHEBI:17815 (ChEBI)
DAPP1ProteinQ9UN19 (Uniprot-TrEMBL)
Dephosphorylated NFATC1/2/3ProteinREACT_119501 (Reactome)
FBXW11 ProteinQ9UKB1 (Uniprot-TrEMBL)
FKBP1A TacrolimusComplexREACT_120070 (Reactome)
FKBP1A ProteinP62942 (Uniprot-TrEMBL)
FYNProteinP06241 (Uniprot-TrEMBL)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
GDP MetaboliteCHEBI:17552 (ChEBI)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRB2-1ProteinP62993-1 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
HRASProteinP01112 (Uniprot-TrEMBL)
IMetaboliteCHEBI:16595 (ChEBI)
IGHDProteinP01880 (Uniprot-TrEMBL)
IGHMProteinP01871 (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)
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)
KRASProteinP01116 (Uniprot-TrEMBL)
LYNProteinP07948 (Uniprot-TrEMBL)
MALT1 ProteinQ9UDY8 (Uniprot-TrEMBL)
MALT1ProteinQ9UDY8 (Uniprot-TrEMBL)
MAP3K7ProteinO43318 (Uniprot-TrEMBL)
NCK1 ProteinP16333 (Uniprot-TrEMBL)
NCK1ProteinP16333 (Uniprot-TrEMBL)
NF-kappa-B p50,/p65,/c-Rel IKBComplexREACT_119154 (Reactome)
NF-kappa-B p50/ p65/c-Rel p-IKBComplexREACT_119527 (Reactome)
NF-kappaB

p-IkB

SCF-betaTrCP		ComplexREACT_119791 (Reactome)
NF-kappaB p50/p65/c-Rel ub-p-IKBComplexREACT_120175 (Reactome)
NF-kappaB p50/p65/c-Rel DimerComplexREACT_118873 (Reactome)
NF-kappaB p50/p65/c-Rel DimerComplexREACT_119326 (Reactome)
NFKB1ProteinP19838 (Uniprot-TrEMBL)
NFKBIA ProteinP25963 (Uniprot-TrEMBL)
NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
NFKBIE ProteinO00221 (Uniprot-TrEMBL)
NRAS ProteinP01111 (Uniprot-TrEMBL)
ORAI1 ProteinQ96D31 (Uniprot-TrEMBL)
Orai1 dimerComplexREACT_24301 (Reactome)
PIMetaboliteCHEBI:16618 (ChEBI)
PIMetaboliteCHEBI:18348 (ChEBI)
PIK3AP1ProteinQ6ZUJ8 (Uniprot-TrEMBL)
PIK3CD PIK3R1ComplexREACT_119117 (Reactome)
PIK3CD PIK3R1ComplexREACT_119537 (Reactome)
PIK3CD ProteinO00329 (Uniprot-TrEMBL)
PIK3R1 ProteinP27986 (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.
PLC gamma1/2ProteinREACT_120292 (Reactome)
PPIA ProteinP62937 (Uniprot-TrEMBL)
PPP3CA ProteinQ08209 (Uniprot-TrEMBL)
PPP3CBProteinP16298 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PRKCB ProteinP05771 (Uniprot-TrEMBL)
PRKCBProteinP05771 (Uniprot-TrEMBL)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6ProteinQ15008 (Uniprot-TrEMBL)
PSMD7ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1ProteinQ92530 (Uniprot-TrEMBL)
Phosphatidylserine MetaboliteCHEBI:18303 (ChEBI)
PhosphatidylserineCHEBI:18303 (ChEBI)
Phosphorylated NFATC1/2/3ProteinREACT_120227 (Reactome)
REL ProteinQ04864 (Uniprot-TrEMBL)
RELA ProteinQ04206 (Uniprot-TrEMBL)
RasGRP1/3ProteinREACT_119242 (Reactome)
SCF-beta-TrCp1/2ComplexREACT_119753 (Reactome)
SH3KBP1 ProteinQ96B97 (Uniprot-TrEMBL)
SHC1 p46/p52ProteinREACT_111758 (Reactome) SHC1 isoforms p46 and p52 are found in B cells (Smit et al. 1994).
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
STIM1 CalciumComplexREACT_119430 (Reactome)
STIM1 TRPC1ComplexREACT_119530 (Reactome)
STIM1 DimerComplexREACT_27372 (Reactome)
STIM1 ProteinQ13586 (Uniprot-TrEMBL)
SYK ProteinP43405 (Uniprot-TrEMBL)
SYKProteinP43405 (Uniprot-TrEMBL)
TRPC1 ProteinP48995 (Uniprot-TrEMBL)
TRPC1ProteinP48995 (Uniprot-TrEMBL)
Tacrolimus MetaboliteCHEBI:61049 (ChEBI)
Ub-21,22-p-S32,S36-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
UbProteinREACT_3316 (Reactome)
VAV1 ProteinP15498 (Uniprot-TrEMBL)
VAV1ProteinP15498 (Uniprot-TrEMBL)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)
p-12S-NFATC1 ProteinO95644 (Uniprot-TrEMBL)
p-13S-NFATC3 ProteinQ12968 (Uniprot-TrEMBL)
p-14S-NFATC2 ProteinQ13469 (Uniprot-TrEMBL)
p-4Y-PIK3AP1 ProteinQ6ZUJ8 (Uniprot-TrEMBL)
p-5Y-BLNK ProteinQ8WV28 (Uniprot-TrEMBL)
p-6Y-CD19 ProteinP15391 (Uniprot-TrEMBL)
p-6Y-SYK ProteinP43405 (Uniprot-TrEMBL)
p-BCL10 ProteinO95999 (Uniprot-TrEMBL)
p-BCL10ProteinO95999 (Uniprot-TrEMBL)
p-CARMA1 OligomerComplexREACT_119302 (Reactome) The coiled coil (CC) domain of CARMA1 interacts with the CC domain on other CARMA1 molecules to form oligomers of unknown stoichiometry.
p-RasGRP1,3 DAGComplexREACT_118884 (Reactome) RasGRP3 binds diacylglycerol via its C1 domain.
p-S157,S161-NFKBIE ProteinO00221 (Uniprot-TrEMBL)
p-S157,S161-Ub-NFKBIE ProteinO00221 (Uniprot-TrEMBL)
p-S177,S181-IKBKB ProteinO14920 (Uniprot-TrEMBL)
p-S19,S23-NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
p-S19,S23-Ub-NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
p-S32,S36-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
p-S559,S644,S652-CARD11ProteinQ9BXL7 (Uniprot-TrEMBL)
p-T133-RASGRP3 ProteinQ8IV61 (Uniprot-TrEMBL)
p-T184-RASGRP1 ProteinO95267 (Uniprot-TrEMBL)
p-T187-MAP3K7 ProteinO43318 (Uniprot-TrEMBL)
p-Y139-DAPP1 ProteinQ9UN19 (Uniprot-TrEMBL)
p-Y188,Y199-CD79A ProteinP11912 (Uniprot-TrEMBL)
p-Y194,Y195,Y272-SHC1-1ProteinP29353-3 (Uniprot-TrEMBL)
p-Y196,Y207-CD79B ProteinP40259 (Uniprot-TrEMBL) By homology with CD79A (Ig-alpha), CD79B (Ig-beta) is presumed to be phosphorylated on tyrosines 196 and 207.
p-Y223,Y551-BTK ProteinQ06187 (Uniprot-TrEMBL)
p-Y239,Y240,Y317-SHC1-2 ProteinP29353-2 (Uniprot-TrEMBL)
p-Y753,Y759,Y1217-PLCG2 ProteinP16885 (Uniprot-TrEMBL)
p-Y771,Y783-PLCG1 ProteinP19174 (Uniprot-TrEMBL)
p21 RAS GDPComplexREACT_2657 (Reactome)
p21 RAS GTPComplexREACT_4782 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
26S proteasomeREACT_118617 (Reactome)
ADPArrowREACT_118598 (Reactome)
ADPArrowREACT_118618 (Reactome)
ADPArrowREACT_118689 (Reactome)
ADPArrowREACT_118716 (Reactome)
ADPArrowREACT_118728 (Reactome)
ADPArrowREACT_118733 (Reactome)
ADPArrowREACT_118834 (Reactome)
ATPREACT_118598 (Reactome)
ATPREACT_118618 (Reactome)
ATPREACT_118689 (Reactome)
ATPREACT_118716 (Reactome)
ATPREACT_118728 (Reactome)
ATPREACT_118733 (Reactome)
ATPREACT_118834 (Reactome)
Activated PKC betaREACT_118598 (Reactome)
Active CalmodulinREACT_118703 (Reactome)
Active IKK complexArrowREACT_118689 (Reactome)
Active IKK complexREACT_118618 (Reactome)
Antigen BCRREACT_118716 (Reactome)
Antigen

p-BCR

SYK		REACT_118728 (Reactome)
Antigen

p-BCR p-SYK

p-BLNK		ArrowREACT_118834 (Reactome)
Antigen

p-BCR p-SYK

p-BLNK		REACT_118566 (Reactome)
Antigen

p-BCR

p-SYK		ArrowREACT_118728 (Reactome)
Antigen

p-BCR

p-SYK		REACT_118728 (Reactome)
Antigen

p-BCR

p-SYK		REACT_118834 (Reactome)
Antigen p-BCRArrowREACT_118716 (Reactome)
Antigen p-BCRREACT_118749 (Reactome)
AntigenREACT_118606 (Reactome)
BCAP SignalosomeArrowREACT_118566 (Reactome)
BCAP SignalosomeREACT_118601 (Reactome)
BCRREACT_118606 (Reactome)
BLKREACT_118716 (Reactome)
BLNK

GRB2 SOS1 CIN85

CBL		REACT_118834 (Reactome)
BLNK ArrowREACT_118566 (Reactome)
BLNK REACT_118781 (Reactome)
BTKREACT_118566 (Reactome)
CALM1REACT_12602 (Reactome)
CARMA1

BCL10 MALT1 TAK1

IKK		REACT_118689 (Reactome)
CARMA1

BCL10 MALT1

TAK1		ArrowREACT_118689 (Reactome)
CARMA1

MALT1

BCL10		REACT_118585 (Reactome)
CARMA1 oligomerREACT_118598 (Reactome)
CD19 VAV1REACT_118566 (Reactome)
CD19 SignalosomeArrowREACT_118566 (Reactome)
CD19 SignalosomeREACT_118828 (Reactome)
CRAC channelREACT_23967 (Reactome)
Ca2+ArrowREACT_118808 (Reactome)
Ca2+REACT_118703 (Reactome)
Ca2+REACT_118748 (Reactome)
Ca2+REACT_12602 (Reactome)
Calcineurin Phosphorylated NFATC1/2/3REACT_118664 (Reactome)
Calcineurin REACT_118703 (Reactome)
Cyclophilin A Cyclosporin ATBarREACT_118664 (Reactome)
DAGArrowREACT_118781 (Reactome)
DAGREACT_118733 (Reactome)
DAGREACT_118748 (Reactome)
DAPP1REACT_118566 (Reactome)
FKBP1A TacrolimusTBarREACT_118664 (Reactome)
FYNREACT_118716 (Reactome)
GRB2-1REACT_118566 (Reactome)
IArrowREACT_118781 (Reactome)
IArrowREACT_12074 (Reactome)
IKKA

IKKB

NEMO		REACT_118585 (Reactome)
IP3 receptor IP3 complexREACT_118808 (Reactome)
IP3 receptor IP3 complexREACT_12074 (Reactome)
IP3 receptor homotetramerREACT_12008 (Reactome)
IREACT_12008 (Reactome)
LYNREACT_118716 (Reactome)
MALT1REACT_118777 (Reactome)
MAP3K7REACT_118585 (Reactome)
NCK1REACT_118566 (Reactome)
NF-kappa-B p50,/p65,/c-Rel IKBREACT_118618 (Reactome)
NF-kappa-B p50/ p65/c-Rel p-IKBArrowREACT_118618 (Reactome)
NF-kappa-B p50/ p65/c-Rel p-IKBREACT_118856 (Reactome)
NF-kappaB

p-IkB

SCF-betaTrCP		REACT_118619 (Reactome)
NF-kappaB p50/p65/c-Rel ub-p-IKBArrowREACT_118619 (Reactome)
Orai1 dimerREACT_23904 (Reactome)
PIK3AP1REACT_118566 (Reactome)
PIK3CD PIK3R1REACT_118566 (Reactome)
PIREACT_118566 (Reactome)
PLC gamma1/2REACT_118566 (Reactome)
PRKCBREACT_118748 (Reactome)
PhosphatidylserineREACT_118748 (Reactome)
Phosphorylated NFATC1/2/3REACT_118703 (Reactome)
REACT_118566 (Reactome) Phosphorylated SYK phosphorylates BLNK (SLP-65, Fu et al. 1998, Chiu et al. 2002) and BCAP (inferred from mouse, Okada et al. 2000). Effector molecules are then recruited: phosphoinositol 3-kinase (PI3K), Phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.
As inferred from chicken DT40 cells and mouse B cells (Okada et al. 2000), phosphorylated BCAP recruits PI3K, which is phosphorylated by a SYK-dependent mechanism (Kuwahara et al. 1996) and produces phosphatidylinositol-3,4,5-trisphosphate (PIP3). PIP3 recruits BAM32 (Marshall et al. 2000) and BTK (de Weers et al. 1994, Baba et al. 2001) via their PH domains. PIP3 also recruits and activates PLC-gamma1 and PLC-gamma2 (Bae et al. 1998). BTK binds phosphorylated BLNK via its SH2 domain (Baba et al. 2001). BTK phosphorylates Phospholipase C gamma-2 (Rodriguez et al. 2001), which activates phospholipase activity (Carter et al. 1991, Roifman and Wang 1992, Kim et al. 2004, Sekiya et al. 2004).
Phosphorylated BLNK recruits PLC gamma, VAV, GRB2, and NCK (Fu and Chan 1997, Fu et al. 1998, Chiu et al. 2002).
SYK phosphorylates SHC which then binds GRB2 (Saxton et al. 1994, Harmer and DeFranco 1997).
CD19 in a stable complex with VAV1 is phosphorylated by Src kinases (inferred from mouse, Xu et al. 2002) and possibly by LYN (inferred from mouse, Fujimoto et al. 2000) in response to BCR activation. Phosphorylated CD19 then binds PI3K (Roifman and Ke 1993, Chalupny et al. 1993, Uckun et al. 1993, Weng et al. 1994, Brooks et al. 2000, Brooks et al. 2004) and can bind PLC-gamma2, which competes with VAV1 for the same binding site on CD19 (Brooks et al. 2000, Brooks et al. 2004).
REACT_118585 (Reactome) TAK1 and the IKK complex are observed to migrate from the cytosol to lipid rafts containing the CARMA1:BCL10:MALT1 (CBM) complex (Sommer et al. 2005, Shinohara et al. 2005 using chicken cells). By analogy with activation of NF-KappaB signaling in T cells, TAK1 in B cells may also be bound to TAB1 and TAB2 or TAB3, which bind K63-conjugated polyubiquitin on a TRAF protein bound to the CBM complex (reviewed in Shinohara et al. 2009).
REACT_118598 (Reactome) CARMA1 is phosphorylated at serines 559, 644, and 652 by Protein Kinase C beta (PKC-beta) (Sommer et al. 2005). CARMA1 is constitutively oligomerized (Tanner et al. 2007) and most CARMA1 in unstimulated cells is cytosolic (Sommer et al. 2005, Tanner et al. 2007), though a portion is constitutively associated with the plasma membrane (Gaide et al. 2002, Sommer et al. 2005). After phosphorylation, CARMA1 is associated with lipid rafts in the plasma membrane (Sommer et al. 2005). Note that some publications refer to CARMA1 with a different N-terminal methionine that is 7 amino acids shorter. In this case the phosphorylated serines are 552, 537, and 645.
REACT_118601 (Reactome) PI3K generates phosphoinositol-3,4,5-trisphosphate (PIP3) from PIP2 after activation of the BCR (Gold et al. 1992, Chantry et al. 1997). Experiments in mice indicate that PI3K associated with BCAP is partly responsible for the activity (Aiba et al. 2008). (PI3K associated with CD19 is also partly responsible (Aiba et al. 2008).)
REACT_118606 (Reactome) Mature, unstimulated B cells express IgM and IgD immunoglobulins on their surfaces (Fu et al. 1974, Fu et al. 1975, reviewed in Kunkel 1975). The immunoglobulins form B cell receptor (BCR) complexes with disulfide-linked heterodimers of Ig-alpha (CD79A) and Ig-beta (CD79B), which have cytoplasmic tails containing immunoreceptor tyrosine-based activation motifs (ITAMs) (van Noesel et al. 1992, Saouaf et al. 1995, inferred from mouse Hombach et al. 1990, Wienands et al. 1990). Upon binding of antigen to the immunoglobulin a chain of phosphorylation events is triggered (Nel et al. 1984, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Harwood and Batista 2010).
REACT_118617 (Reactome) Phosphorylated, ubiquitinated IkB is degraded by the proteasome (Miyamoto et al. 1994, Traenckner et al. 1994, Alkalay et al. 1995, DiDonato et al. 1995, Li et al. 1995, Lin et al. 1995, Scherer et al. 1995, Chen et al. 1995). IkB does not dissociate from NF-kB before it is proteolyzed (Miyamoto et al. 1994, Traenckner et al. 1994, DiDonato et al. 1995, Lin et al. 1995).
REACT_118618 (Reactome) Activated IKK complex phosphorylates the I-kappaB component of the cytoplasmic NF-kappaB complex (Zandi et al. 1998, Burke et al. 1999, Heilker et al. 1999). B cells contain I-kappaB-alpha, I-kappaB-beta, and I-kappaB-epsilon (Whiteside et al. 1997, Li and Nabel 1997).
REACT_118619 (Reactome) SKP:Cul:F-box (SCF) complexes containing F-box factors Beta-TrCP1 (BTRCP, E3RSIkappaB) or beta-TrCP2 (BTRCP2, FBXW11, HOS) catalyze the polyubiquitination of IkappaB (Yaron et al. 1998, Fuchs et al. 1999, Suzuki et al. 1999, Tan et al. 1999, Winston et al. 1999, Wu and Ghosh 1999).
REACT_118664 (Reactome) As inferred from mouse (Okamura et al. 2000), calcineurin dephosphorylates NFATC2 at 13 serine residues (Batiuk et al. 1997, Kim et al. 2000). B lymphocytes also contain NFATC2 and NFATC3 which are inferred to undergo dephosphorylation at homologous serines. Dephosphorylation of NFATs exposes a nuclear localization signal which cause NFATs to be imported into the nucleus (Kim et al. 2000). In mouse, Calcineurin is observed to also transit into the nucleus in a complex with NFATs and may remain associated (Shibasaki et al. 1996).
REACT_118688 (Reactome) TRPC1 forms a channel that transports Ca2+ across the plasma membrane. TRPC1 is gated by STIM1 (Ong et al. 2007).
REACT_118689 (Reactome) TAK1 phosphorylates IKK-beta (Wang et al. 2001). As inferred from chicken B cells, the reaction in human B cells may occur when TAK1 and the IKK complex are associated with the CARMA1:BCL10:MALT1 (CBM) complex. During T cell activation TAK1 forms a complex with TAB1 and TAB2, which binds K-63 conjugated polyubiquitin attached to TRAF6 associated with the CBM complex (Sun et al. 2004, reviewed in Shinohara et al. 2009). TRAF6 also polyubiquitinates IKK-gamma in T cells (Zhou et al. 2004). B cells contain functional TRAF6 and TRAF2 (Zhang et al. 2010) so the same mechanism may occur during activation of B cells.
REACT_118703 (Reactome) Calcium activates calcineurin in two ways: binding the regulatory subunit of calcineurin directly and binding calmodulin which then interacts with the catalytic subunit of calcineurin. As inferred from mouse, B lymphocytes contain the R1 regulatory subunit (PPP3R1) and the beta catalytic subunit (PPP3CB).
In the presence of calcium and calcium:calmodulin calcineurin binds phosphorylated and unphosphorylated NFATs at 2 regions in the N-terminus (Luo et al. 1996, Garcia-Cozar et al. 1998, Park et al. 2000, evidence from mouse in Loh et al. 1996 and Wesselborg et al. 1996). Calcineurin also weakly interacts with NFATs in the absence of calcium (Garcia-Cozar et al. 1998).
REACT_118705 (Reactome) Nf-kappaB subunits contain nuclear localization sequences and, in the absence of IkB, are translocated to the nucleus (Bauerle and Baltimore 1988, Blank et al. 1991, Ghosh et al. 2008, Fagerlund et al. 2008). c-Rel binds to importins alpha5, alpha6, and alpha7; RelB binds to importins alpha5 and alpha6; p52 binds importin alpha3, alpha4, alpha5, and alpha6 (Fagerlund et al. 2008)
REACT_118716 (Reactome) The B cell receptor (BCR) comprises an immunoglobulin complexed with a heterodimer of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29). After immunoglobulin IgM or IgD binds antigen the associated Ig-alpha and Ig-beta are each observed to be phosphorylated at two tyrosine residues in the cytoplasmic immunoreceptor tyrosine-activated motif (ITAM) (Sanchez et al. 1993, Hata et al. 1994, Saouaf et al. 1994, Saouaf et al. 1995). Saouaf et al. (1995) showed that the kinase Blk could phosphorylate both tyrosines of each ITAM and that the kinase SYK specifically bound phosphorylated but not unphosphorylated ITAMs. In mouse the kinase Lyn and other kinases phosphorylate one tyrosine and Syk is believed to phosphorylate the other (Yamanashi et al. 1991, Flaswinkel and Reth 1994, Rolli et al. 2002).
REACT_118728 (Reactome) The SYK protein tyrosine kinase autophosphorylates at tyrosines 131, 323, 348, 352, 525, and 526 (Law et al. 1994, Rowley et al. 1995, Baldock et al. 2000, Irish et al. 2006, Papp et al. 2007, Chen et al. 2008, Tsang et al. 2008). The autophosphorylation increases the kinase activity of SYK. SYK is also phosporylated on additional residues in response to BCR activation (Bohnenberger et al. 2011).
REACT_118733 (Reactome) RasGRP1 and RasGRP3 translocate to the plasma membrane where they bind diacylglycerol (Lorenzo et al. 2001) and are phosphorylated (Teixeira et al. 2003, Zheng et al. 2005). Though RasGRP3 is phosphorylated in vitro and in some cell lines (e.g. Ramos cells) by protein kinase C theta (PKC-theta, Zheng et al. 2005), normal B cells do not contain PKC-theta (Meller et al. 1999). Both Rasgrp1 and Rasgrp3 participate in activating Ras in response to BCR signaling in mouse B cells (Coughlin et al. 2005).
REACT_118748 (Reactome) Human Protein kinase C beta (PKC-beta) is activated by calcium ions, diacylglycerol, and binds phosphatidylserine (Kochs et al. 1991). Experiments in mice have shown that knocking out PKC-beta causes severe defects in B cells, leading to the conclusion that PKC-beta is the predominant signaling PKC in these cells (Leitges et al. 1996, Su et al. 2002, Saijo et al. 2002).
REACT_118749 (Reactome) The SYK protein tyrosine kinase binds specifically to phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Law et al. 1994, Saouaf et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding activates the kinase activity of SYK (Rowley et al. 1995, Tsang et al. 2008).
REACT_118759 (Reactome) The polybasic region of STIM1 interacts with 2 aspartate residues in the C-terminal region of TRPC1 (Zeng et al. 2008, Huang et al. 2006). The STIM1:TRPC1 complex can form a tenary complex with ORAI1 (Ong et al. 2007, Jardin et al. 2008) and ORAI participates in function of STIM1:TRPC1 channels (Cheng et al. 2008, Cheng et al. 2011). As inferred from chicken DT40 cells, TRPC1 (and possibly other TRP channels) participates in store-operated calcium influx during signaling by the B cell receptor (Mori et al. 2002).
REACT_118777 (Reactome) CARMA1 is phosphorylated and recruits BCL10 and MALT1 to the plasma membrane to form the CBM complex (Sommer et al. 2005, Tanner et al. 2007). Evidence from T cells (Jurkat cells) indicates that MALT1 and BCL10 oligomerize to activate the IKK complex (Zhou 2004).
REACT_118781 (Reactome) Phospholipase C gamma (PLC-gamma) is activated by phosphorylation in response to antigen-binding by the B cell receptor (Carter et al. 1991, Roitman and Wang 1992, Rodriguez et al. 2001, Kim et al. 2004, Sekiya et al. 2004). Phospholipase C gamma hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate and diacylglycerol (Carter et al. 1991, Kim et al. 2004). Human B cells contain both PLC-gamma1 and PLC-gamma2, with PLC-gamma2 predominating (Coggeshall et al. 1992).
REACT_118807 (Reactome) RasGRP1 (Roose et al. 2007) and RasGRP3 (Ohba et al. 2000, Yamashita et al. 2000, Rebhun et al. 2000, Lorenzo et al. 2001) catalyze the exchange of GDP for GTP bound by RAS.
REACT_118808 (Reactome) In the resting state the luminal domain of STIM1 binds Ca2+ ions within the endoplasmic reticulum and this binding prevents dimerization of STIM1 (Luik et al. 2008). Upon depletion of Ca2+ ions from the endoplasmic reticulum, STIM1 is no longer bound to Ca2+ and forms homodimers (Muik et al. 2008, Luik et al. 2008, Park et al. 2009).
REACT_118828 (Reactome) PI3K generates phosphoinositol-3,4,5-trisphosphate (PIP3) from PIP2 after activation of the BCR (Gold et al. 1992). Experiments in mice indicate that PI3K associated with CD19 is partly responsible for the activity (Buhl et al. 1997, Otero et al. 2001, Aiba et al. 2008). (PI3K associated with BCAP is also partly responsible (Aiba et al. 2008).)
REACT_118834 (Reactome) BLNK (SLP-65, BASH) forms a stable complex with GRB2, SOS1, and CIN85 in the cytosol. The complex is recruited to the plasma membrane where activated (phosphorylated) SYK phosphorylates BLNK at tyrosines 72, 84, 96, 178, and 189 (Fu et al. 1998, Chiu et al. 2002, inferred from mouse in Wienands et al. 1998, from chicken in Oellerich et al. 2009). Phosphorylated BLNK serves as a scaffold that binds effector molecules such as Phospholipase C. As inferred from mouse, BLNK interacts with phosphorylated tyrosines on CD79A (Ig-alpha) (Engels et al. 2001, Kabak et al. 2002).
REACT_118856 (Reactome) SKP:Cul:F-box (SCF) complexes containing F-box factors Beta-TrCP1 (BTRCP, E3RSIkappaB) or beta-TrCP2 (BTRCP2, FBXW11, HOS) bind IkappaB (Yaron et al. 1998, Fuchs et al. 1999, Suzuki et al. 1999, Tan et al. 1999, Winston et al. 1999, Wu and Ghosh 1999).
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_12602 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions.
REACT_23904 (Reactome) Sustained calcium signalling in lymphocytes and platelets requires the uptake of extracellular calcium when intracellular stores are depleted. The process whereby intracellular calcium depletion stimulates calcium uptake is often referred to as Store-operated calcium entry (SOCE). Store depletion is sensed by stromal interaction molecule 1 (STIM1), which then translocates to the plasma membrane and associates with 2 dimers of Orai1 to form a calcium-release activated calcium (CRAC) channel.
REACT_23967 (Reactome) Activation of Calcium-release-activated (CRAC) channels allows influx of calcium. The Orai component of CRAC is responsible for the selectivity of the channel, while the Stim component is responsible for activation.
RasGRP1/3REACT_118733 (Reactome)
SCF-beta-TrCp1/2ArrowREACT_118619 (Reactome)
SCF-beta-TrCp1/2REACT_118856 (Reactome)
SHC1 p46/p52REACT_118566 (Reactome)
STIM1 TRPC1REACT_118688 (Reactome)
STIM1 DimerArrowREACT_118808 (Reactome)
STIM1 DimerREACT_118759 (Reactome)
STIM1 DimerREACT_23904 (Reactome)
SYKREACT_118749 (Reactome)
TRPC1REACT_118759 (Reactome)
UbREACT_118619 (Reactome)
VAV1REACT_118566 (Reactome)
p-BCL10REACT_118777 (Reactome)
p-CARMA1 OligomerArrowREACT_118598 (Reactome)
p-CARMA1 OligomerREACT_118777 (Reactome)
p-RasGRP1,3 DAGArrowREACT_118733 (Reactome)
p-RasGRP1,3 DAGREACT_118807 (Reactome)
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