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

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10, 11, 20, 26, 35...6, 7, 28, 47, 66...19, 44, 65, 69, 70, 1109, 22, 125, 14714, 26, 48, 50, 53...11, 24, 42, 59, 75...46, 104, 112, 128, 1462, 8, 54, 73, 100...4, 5, 21, 27, 34...15, 84, 96, 115, 12139, 45, 63, 101, 11112, 60, 72, 81, 126...77, 124, 13431, 68, 84, 85, 9930, 40, 41, 83, 95...77, 124, 134104, 112, 12820, 48, 80, 82, 102...63, 67, 9716, 35, 58, 79, 113...97, 101, 1113, 13, 18, 123, 13979, 113, 119, 13042, 48, 90, 13732, 78, 109, 118972, 8, 54, 73, 100...1, 23, 51, 91, 141p-PLC gamma1,2PIP3 CD19VAV1 p21 RASGTP Calcineurin p-BLNKGRB2SOS1CIN85CBL cytosolCARMA1MALT1BCL10 BLNK NF-kappaB p50c-Relp-IKB IP3 receptors p-SHC1 p46/p52 Ig Lambda C region NF-kappaB p50p50 IgD Heavy Chain CARMA1BCL10MALT1TAK1 IgM p-CARMA1 Oligomer NF-kappaB p65p65 IP3 receptors Immunoglobulin Kappa Light Chain p-CARMA1 Oligomer IgM Heavy Chain NF-KappaB p50p50p-IKBA Ig Antibody Light Chain NF-kappaB p65p65ub-p-IkB p-BCR PIK3CDPIK3R1 Immunoglobulin Lambda Light Chain CRAC channel Ig Lambda C region Ig Kappa Light Chain V Region Immunoglobulin Kappa Light Chain AntigenBCR IKB alpha/beta/epsilon NF-KappaB p50p50IKBA IgM Antigenp-BCRSYK IgM Heavy Chain IgM or IgD IgD Heavy Chain NF-kB complex IgM Heavy Chain Antigenp-BCRp-SYK SCF-beta-TrCP2 complex Ig Heavy Chain V Region Antigenp-BCR Ig Lamda Light Chain V Region Ig Antibody Light Chain NF-KappaB p50p50ub-p-IKBA NF-kappaB p65p65 PPP3CA/BFe3+Zn2+ Ig Antibody Light Chain NF-kappaB p65p65IKB NF-kB complex IgM Heavy Chain NF-kappaB p50/p65/c-Relub-p-IKB Ig Lamda Light Chain V Region BCR Ig Antibody Light Chain IgM or IgD p-BCR IgD Active Calmodulin CARMA1 oligomer Ig Lambda C region Ig Lamda Light Chain V Region PIK3CDPIK3R1 NF-kappaB p50p50 Ig Antibody Light Chain Antigenp-BCR CARMA1MALT1BCL10 Ig Heavy Chain V Region NF-kappaB p65p65p-IKB Ig Lamda Light Chain V Region NF-kappaB p50/p65/c-Rel Dimer NF-kappaB p50p65p-IKB NF-kappaB p65p65p-IKB IP3 receptorIP3 complex Antigenp-BCR IgM or IgD NF-kappa-B p50,/p65,/c-RelIKB PPP3CA/BCalmodulin p-BLNKGRB2SOS1CIN85CBL IP3 receptor homotetramer p-RasGRP1,3DAG IgM or IgD NF-kappaB p50p65p-IKB CD19 Signalosome Ig Kappa Light Chain V Region NF-kappaB p50c-Rel STIM1 Dimer Immunoglobulin Lambda Light Chain NF-kappaBp-IkBSCF-betaTrCP IgD Heavy Chain NF-kappa-B p50/ p65/c-Relp-IKB p-BAM32PIP3 IgM Heavy Chain Immunoglobulin Lambda Light Chain Ig Lamda Light Chain V Region IgD p-BCR Ig Heavy Chain V Region Immunoglobulin Kappa Light Chain NF-kappaB p65p65 Immunoglobulin Kappa Light Chain NF-kappa-B p50/ p65/c-Relp-IKB PPP3CA/B p21 RASGDP NF-kappaB p50p50 p-IKB alpha/beta/epsilon Ig Lambda C region Ig Lambda C region STIM1Calcium IgD Heavy Chain NF-kappaB p50c-RelIkB Orai1 dimer IgM IgD NF-kappaB p50p50 NF-kappaB p50c-Rel BCAP Signalosome Antigenp-BCR p-BCR Ig Kappa Light Chain V Region IKKAIKKBNEMO PPP3CA/B PPP3CA/BFe3+Zn2+ Antigenp-BCR Calcineurin alpha regulatory subunitCalcium IgM or IgD 26S proteasome IgM Immunoglobulin Kappa Light Chain Orai1 dimer SCF-beta-TrCP2 complex NF-kB complex Ig Heavy Chain V Region Ig Kappa Light Chain V Region IgM Heavy Chain NF-kappaB p65p65 NF-KappaB p50p50p-IKBA ub-p-IKB alpha/beta/epsilon BCR Ig Antibody Light Chain IgD Heavy Chain p21 RAS Cyclophilin ACyclosporin A Immunoglobulin Kappa Light Chain CalcineurinPhosphorylated NFATC1/2/3 NF-kappaB p50p50 IgM Ig Kappa Light Chain V Region PIK3CDPIK3R1 IgM or IgD NF-kB complex Immunoglobulin Lambda Light Chain SCF-beta-TrCp1/2 NF-kappaB p65p65 NF-kappaB p65p65 NF-kappaB p50p50 NF-kappaB p50c-Relp-IKB NF-kappaB p50c-Rel Ig Lamda Light Chain V Region NF-kappaB p50c-Rel Ig Lamda Light Chain V Region Antigenp-BCRp-SYKp-BLNK endoplasmic reticulum lumennucleoplasmIgM IgD Heavy Chain IgM or IgD Antigenp-BCRp-SYK STIM1 Dimer NF-kappaB p50p65ub-p-IKB Ig Kappa Light Chain V Region Phosphorylated NFATC1/2/3 Antigenp-BCRp-SYK NF-kB complex IgD IgM Active IKK complex IgD p-RasGRP1/3 p21 RAS p-BCR IgD Heavy Chain Ig Heavy Chain V Region Ig Heavy Chain V Region IgM Heavy Chain Immunoglobulin Lambda Light Chain plasma membraneImmunoglobulin Kappa Light Chain SCF-beta-TrCp1/2 CalcineurinCalmodulin p-CARMA1 Oligomer Ig Heavy Chain V Region p-CARMA1 Oligomer IKKAIKKBNEMO NF-kappaB p50p65IKB NF-kappaB p50/p65/c-Rel Dimer CARMA1MALT1BCL10 Ig Lambda C region STIM1TRPC1 BLNKGRB2SOS1CIN85CBL Ig Kappa Light Chain V Region SCF-beta-TrCP1 complex Activated PKC beta p-PLC gamma1/2 p-IKB alpha/beta/epsilon CARMA1BCL10MALT1TAK1IKK IgD NF-kappaB p50c-Rel Antigenp-BCRp-SYKp-BLNK Immunoglobulin Lambda Light Chain Ig Lambda C region Active Calmodulin FKBP1ATacrolimus Immunoglobulin Lambda Light Chain p-BTKPIP3 IgD NF-kB complex SCF-beta-TrCP1 complex Ig Antibody Light Chain STIM1 Dimer NF-kappaB p50c-Relub-p-IKB NF-kappaB p50c-Rel PIK3CDPIK3R1 IP3 receptor homotetramer PSMF1Ig kappa chain V-III region POM Ig lambda chain V-II region NIG-84 Ig heavy chain V-III region BRO Ig lambda chain V-I region BL2 p-12S-NFATC1 CBLB Ig heavy chain V-II region DAW Ig heavy chain V-I region SIE Ig heavy chain V-II region COR IGKV4-1Ig kappa chain V-III region WOL Ig kappa chain V-I region Roy CARMA1BCL10MALT1TAK1IKKIg lambda chain V-II region TOG Ig kappa chain V-III region B6 Ig heavy chain V-II region COR Ig lambda chain V-I region HA Ig lambda chain V-III region LOI Ig kappa chain V-II region TEW Ig heavy chain V-III region JON Ig lambda chain V-IV region Kern Ig heavy chain V-III region GA PRKCB Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-III region KOL Ig heavy chain V-II region DAW LYNSYKp-Y196,Y207-CD79B IGKV1-5Ig kappa chain V-I region DEE IGHVIg lambda chain V-III region LOI PSMC5 Ig kappa chain V-IV region STH Ig heavy chain V-III region POM Ig heavy chain V-III region TUR Ig heavy chain V-III region BUT p-S157,S161-Ub-NFKBIE Ig heavy chain V-I region HG3 Ig kappa chain V-I region EU PSMB1 Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-II region HE BLNKGRB2SOS1CIN85CBLIg kappa chain V-IV region B17 Ig lambda chain V-II region WIN Ig lambda chain V-IV region X Ig lambda chain V-VI region WLT Ig heavy chain V-II region COR Ig kappa chain V-I region Rei IGLC7Ig heavy chain V-II region WAH p21 RASGTPIg heavy chain V-I region EU Ig kappa chain V-II region RPMI 6410 Ubp-6Y-SYK Ig lambda chain V-II region WIN SYK Ig heavy chain V-III region TEI Ig heavy chain V-III region DOB Ig lambda chain V-I region WAH p-BCL10 Ig kappa chain V-III region SIE Ig heavy chain V-I region HG3 PSMD14 Ig lambda chain V-VI region AR MAP3K7Ig kappa chain V-IV region JI CBL Ig heavy chain V-III region CAM Ig heavy chain V-III region BUT Ig lambda chain V-I region MEM SOS1 Ig heavy chain V-II region MCE Fe3+ IGHDIg heavy chain V-III region TEI REL Ig kappa chain V-I region EU Ig lambda chain V-II region NIG-58 Ig lambda chain V-III region SH CHUK Ig heavy chain V-II region NEWM NF-kappa-B p50/ p65/c-Relp-IKBIg heavy chain V-II region COR Ig lambda chain V-VII region MOT Ig lambda chain V-I region MEM NF-kappaB p50/p65/c-Rel DimerPIK3CDPIK3R1Ig kappa chain V-III region Ti GTP SHC1 p46/p52Ig heavy chain V-I region ND Ig kappa chain V region EV15 Ig lambda chain V-I region NEWM Ig heavy chain V-III region CAM Ig lambda chain V-IV region Bau Ig lambda chain V-I region NIG-64 IGHMIg heavy chain V-II region ARH-77 Ig kappa chain V-III region WOL Ig kappa chain V-III region HAH Ig lambda chain V-III region SH Ig kappa chain V-III region IARC/BL41 Ig lambda chain V-VII region MOT PSME3 p-T187-MAP3K7 Ig lambda chain V-II region VIL Ig lambda chain V-VI region NIG-48 Ig heavy chain V-III region BRO Ig kappa chain V-I region CAR PLC gamma1/2Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-IV region Hil Ca2+ Ig lambda chain V-II region BO Ig heavy chain V-I region EU Ig lambda chain V-II region NEI Ig heavy chain V-II region OU Ig lambda chain V region 4A Ig kappa chain V-III region IARC/BL41 Ig kappa chain V-I region Mev Ig heavy chain V-II region OU TRPC1 IGLC3PIK3R1 Ig heavy chain V-II region HE CUL1 Ig kappa chain V-I region Mev Ig kappa chain V-III region HIC Ig kappa chain V-I region HK101 PIIg kappa chain V-III region B6 Ig heavy chain V-III region GAL Ig kappa chain V-I region AU IGHV7-81IGHMIg kappa chain V-I region WEA Ig kappa chain V-I region Wes CD79A IGHMIg lambda chain V-I region BL2 Ig kappa chain V-II region MIL BTRC Ig lambda chain V-I region WAH FYNIg kappa chain V-II region MIL Ig lambda chain V-V region DEL Ig lambda chain V-VI region WLT Ig kappa chain V-I region Bi Ig heavy chain V-III region BUR Ig kappa chain V-III region B6 Ig kappa chain V-I region Scw ADPIg lambda chain V-IV region MOL RELA NRAS Ig heavy chain V-III region TRO IgH heavy chain V-III region VH26 precursor ATPIg kappa chain V-I region Daudi Ig kappa chain V-I region Lay HRASADPIg heavy chain V-I region ND Ig heavy chain V-II region DAW Ig lambda chain V-III region SH Ig heavy chain V-III region WAS VAV1 Ig kappa chain V-III region WOL PPP3CBAntigenp-BCRp-SYKp-6Y-CD19 Ig kappa chain V-III region HIC IGKCATPIg lambda chain V-I region NEWM ADPp-T187-MAP3K7 CALM1 Ig lambda chain V-II region BOH Ig heavy chain V-III region BUR Ig heavy chain V-III region POM p-Y188,Y199-CD79A Ig lambda chain V-IV region X Ig lambda chain V-VI region AR Ig kappa chain V-I region Bi Ig kappa chain V-III region VH Ig kappa chain V-I region OU p-5Y-BLNK Ig lambda chain V-I region VOR CD19VAV1IGHV7-81Ig heavy chain V-III region GAL Ig heavy chain V-III region LAY VAV1 IIg heavy chain V-III region WEA Ig heavy chain V-II region NEWM Ig lambda chain V-III region SH Ig kappa chain V-I region Mev Ig lambda chain V-II region VIL Ig heavy chain V-III region WAS Ig kappa chain V-II region GM607 Ig kappa chain V-II region MIL IGKV1-5IgH heavy chain V-III region VH26 precursor Ig lambda chain V-II region NEI Ig kappa chain V-IV region B17 Ig kappa chain V-IV region B17 Ig kappa chain V-I region HK101 Ig kappa chain V-I region Bi Ig heavy chain V-III region TUR CRAC channelPSMB8 PIK3AP1Ig kappa chain V-III region SIE STIM1 Ig lambda chain V-I region NIG-64 p-S19,S23-Ub-NFKBIB Ig kappa chain V-I region AG Ig heavy chain V-III region BUR IGLC3Ig kappa chain V-I region BAN Ig lambda chain V-I region NIG-64 Ig kappa chain V-III region WOL p-S19,S23-NFKBIB Ig kappa chain V-I region Hau Ig heavy chain V-I region ND Ig kappa chain V-III region SIE IGKVA18Ig lambda chain V-I region EPS KRASADPPIK3R1 Ig lambda chain V-II region NIG-84 NF-kappaB p50/p65/c-Rel DimerIg lambda chain V-III region LOI Ig lambda chain V-VI region EB4 Ig lambda chain V-II region BUR Ig heavy chain V-III region TIL Ig heavy chain V-III region POM Ig lambda chain V-II region BUR Fe3+ Ig lambda chain V-II region BO Ig kappa chain V-I region Gal Ig kappa chain V-III region CLL p-Y188,Y199-CD79A Ig kappa chain V-II region Cum NFKB1Ig lambda chain V-I region NEW Ig lambda chain V-VI region AR CARMA1 oligomerIg kappa chain V region EV15 ATPIg kappa chain V-III region POM Ig kappa chain V-I region Gal AntigenBCRIg kappa chain V-I region WEA Ig kappa chain V-I region Walker Ig heavy chain V-II region NEWM Zn2+ NF-kappaB p50/p65/c-Relub-p-IKBIg lambda chain V-IV region MOL Ig kappa chain V-IV region B17 MALT1DAPP1Ig lambda chain V-I region HA IGLC3Ig heavy chain V-III region TRO Ig heavy chain V-III region POM Ig heavy chain V-III region DOB Ig heavy chain V-III region JON Ig kappa chain V-I region WAT Dephosphorylated NFATC1/2/3Ig lambda chain V-IV region Kern Ig kappa chain V-III region POM Ig heavy chain V-I region EU Ig lambda chain V-II region TOG Ig lambda chain V-IV region Hil Ig lambda chain V-II region MGC Ig lambda chain V-II region WIN Ig kappa chain V-I region Wes Ig kappa chain V-II region FR Ig kappa chain V-I region AU IGHV7-81Ig kappa chain V-I region OU Ig lambda chain V-I region VOR Ig heavy chain V-III region HIL Cyclophilin ACyclosporin AIg lambda chain V-VI region WLT 26S proteasomeIg kappa chain V-I region Bi Ig heavy chain V-III region HIL REL Ig kappa chain V-I region Daudi Ig kappa chain V-I region EU IGHMIg kappa chain V-I region Roy IGLC2Ig heavy chain V-III region KOL Ig heavy chain V-III region NIE Ig kappa chain V-I region DEE Ig kappa chain V-III region IARC/BL41 IGLC6Ig heavy chain V-III region GAL Ig lambda chain V-I region VOR Ig heavy chain V-III region DOB PSME4 Ig lambda chain V-V region DEL PSMA6 FKBP1A Ig heavy chain V-I region EU PSMA8 SH3KBP1 Ig heavy chain V-III region NIE Ig kappa chain V-III region SIE Ig kappa chain V-I region Kue Ig kappa chain V-III region VG Ig kappa chain V-III region IARC/BL41 Ig lambda chain V-II region VIL PSMB9 Ig kappa chain V-I region Ni Ig kappa chain V-I region Wes Ig kappa chain V-IV region JI Ig kappa chain V-I region Ka p-Y188,Y199-CD79A Ig lambda chain V-I region NIG-64 PPP3CBIGKV1-5Ig lambda chain V-II region MGC Ig lambda chain V-I region EPS Ig lambda chain V-I region BL2 Ig lambda chain V-II region NIG-84 NFKBIB IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Kue Ig kappa chain V-I region Gal Ig kappa chain V-III region NG9 Ig kappa chain V-III region GOL p-S559,S644,S652-CARD11Ig heavy chain V-I region SIE IGKCIg heavy chain V-I region Mot Ig kappa chain V-I region Daudi Ig kappa chain V-I region Bi Ig lambda chain V-I region EPS Ig heavy chain V-III region BUT Ig kappa chain V region EV15 Ig lambda chain V-IV region MOL Ig lambda chain V-II region TOG Ig lambda chain V region 4A IGLC7Ig kappa chain V-III region NG9 Ig kappa chain V-III region Ti PIK3CD p-S157,S161-NFKBIE Ig kappa chain V-I region Walker Ig heavy chain V-III region WAS Ig lambda chain V-V region DEL IGKV1-5Ig kappa chain V-I region WAT Ig lambda chain V-I region HA Ig kappa chain V-III region SIE Ig heavy chain V-III region KOL Ig kappa chain V-III region GOL CBLB IGKVA18IGLVIP3 receptor homotetramerIg lambda chain V-I region NEWM IGKCIg lambda chain V region 4A NCK1PSMA7Ig lambda chain V-II region MGC Ig lambda chain V-II region TRO Ig kappa chain V-I region Roy Ig heavy chain V-I region WOL Ig heavy chain V-II region MCE Ig heavy chain V-III region WAS PSMA1 Ig lambda chain V-IV region Hil Ig lambda chain V-I region NIG-64 CALM1p-BCL10Ig lambda chain V-II region BUR REL IGHV7-81Ig heavy chain V-III region WEA Ig kappa chain V-II region FR Ig kappa chain V-III region CLL IGLC6Ig heavy chain V-III region WAS Ig heavy chain V-I region Mot BLNK Ig lambda chain V-II region BOH DAG Ig heavy chain V-I region SIE Ig heavy chain V-III region ZAP Ig heavy chain V-II region OU Ig heavy chain V-III region KOL Ig kappa chain V-I region OU Ig lambda chain V-IV region Bau IGHDPSMA4 CalcineurinPhosphorylated NFATC1/2/3Ig kappa chain V-IV region B17 Ig heavy chain V-I region ND Ig kappa chain V-I region Scw Ig lambda chain V-I region VOR CARMA1BCL10MALT1TAK1Ig kappa chain V-III region GOL Ig kappa chain V-I region Scw Ig kappa chain V-I region Kue Antigenp-BCRp-SYKp-BLNKIg lambda chain V-VI region SUT Ig lambda chain V-IV region X PSMA3 Ig heavy chain V-III region WAS Ig heavy chain V-III region TUR NRAS PIK3CD Ig kappa chain V-IV region Len GRB2-1PIK3R1 Ig kappa chain V-I region Ni Ig heavy chain V-III region BUT Ig kappa chain V-I region Mev Ig lambda chain V-VI region WLT Ig kappa chain V-I region Wes Ig heavy chain V-III region NIE Ig heavy chain V-III region WEA Ig lambda chain V-I region NIG-64 PSMC1Ig kappa chain V-I region OU Ig lambda chain V-II region BUR Ig lambda chain V-I region HA Ig kappa chain V-I region Ka Ig kappa chain V-I region AG RELA Ig heavy chain V-II region HE Ig lambda chain V-II region NIG-58 IGHDIg lambda chain V-IV region Bau Ig kappa chain V-III region NG9 Ig heavy chain V-II region ARH-77 Activated PKC betaIg heavy chain V-III region ZAP Ig kappa chain V-I region BAN Ig kappa chain V-III region VG IGLVIg lambda chain V-II region TOG Ig kappa chain V-IV region Len Ig kappa chain V-I region DEE p-S177,S181-IKBKB Ig heavy chain V-III region HIL IGLC6IGKV1-5Ig heavy chain V-II region MCE PSMC2 ITPR3 ATPIg kappa chain V-I region Gal Ig kappa chain V-I region Daudi Ig kappa chain V-I region Walker Ig heavy chain V-III region ZAP Ig kappa chain V-II region Cum Ig kappa chain V-I region DEE Ig heavy chain V-III region HIL Ig lambda chain V-IV region X p-13S-NFATC3 Ig heavy chain V-III region ZAP Ig lambda chain V-II region NIG-58 AntigenIg lambda chain V-II region NIG-84 IGLC1PSMB2 Ig lambda chain V-II region BOH Antigenp-BCRIg lambda chain V-II region NIG-84 Ig kappa chain V-II region TEW Ig heavy chain V-I region WOL Ig lambda chain V-II region BUR Ca2+Ig heavy chain V-III region JON p-S32,S36-NFKBIA Ig kappa chain V-II region TEW RELA Ig kappa chain V-II region RPMI 6410 Ig kappa chain V-I region WAT Ig lambda chain V-II region BO PSMD1 Ig kappa chain V-III region GOL Ig lambda chain V-I region MEM Ig heavy chain V-III region GAL Ig heavy chain V-I region WOL Ig lambda chain V-II region BUR Ig kappa chain V-I region Kue Ig heavy chain V-II region WAH CD19 IGLVIg lambda chain V-V region DEL FBXW11 CD79A Ig lambda chain V-VI region SUT PhosphatidylserineIg heavy chain V-I region HG3 Ig kappa chain V-III region HAH Ig kappa chain V-IV region JI REL Ig lambda chain V-II region BUR p-S559,S644,S652-CARD11Ig kappa chain V-II region GM607 Ig kappa chain V-III region WOL Ig kappa chain V-I region Lay Ig lambda chain V-II region NEI Ig lambda chain V-III region SH Ig heavy chain V-I region HG3 SH3KBP1 Ig kappa chain V-I region WEA Ig kappa chain V-I region Scw Ig kappa chain V-I region CAR Ig lambda chain V-VI region WLT Ig heavy chain V-I region Mot IGLC3Ig kappa chain V-I region EU NF-kappa-B p50,/p65,/c-RelIKBIg lambda chain V-VI region WLT PSMD12 p-BCL10 Ig lambda chain V region 4A p-T184-RASGRP1 Ig heavy chain V-I region Mot CALM1 Ig heavy chain V-III region LAY Ig lambda chain V-I region MEM Ig kappa chain V-II region FR PIK3R1 IGLC2CBL Ig heavy chain V-III region TEI Active IKK complexIg lambda chain V-IV region X Ig kappa chain V-I region Mev ATPIg heavy chain V-III region BUR Ig heavy chain V-III region TRO Ig kappa chain V-I region Scw Ig kappa chain V-II region FR Ig lambda chain V-II region BOH Ig kappa chain V-III region VG Ig heavy chain V-III region POM Ig kappa chain V-III region B6 Ig heavy chain V-III region NIE Ig heavy chain V-II region HE Ig kappa chain V-II region GM607 Ig kappa chain V-III region VG NF-kappaBp-IkBSCF-betaTrCPPSMD6Ig kappa chain V-III region CLL Ig kappa chain V-II region FR IGKVA18Ig lambda chain V-II region TRO NFKBIA Ig heavy chain V-III region TIL GDP Ig lambda chain V-VI region EB4 Ig kappa chain V-I region Roy Ig heavy chain V-II region MCE NFKB1p-Y223,Y551-BTK p-Y196,Y207-CD79B Ig lambda chain V-VII region MOT Ig heavy chain V-II region ARH-77 CBLB Ig lambda chain V-II region VIL Ig kappa chain V-IV region JI IGKVA18NCK1 Ig lambda chain V-II region TRO p-T133-RASGRP3 Ig lambda chain V-IV region MOL Ig kappa chain V-III region IARC/BL41 Ig heavy chain V-II region DAW Ig lambda chain V-II region TRO Ig lambda chain V-V region DEL Ig kappa chain V-IV region JI IGLC2Ig heavy chain V-I region SIE Ig kappa chain V-I region AU Ig lambda chain V-I region NEW Ig lambda chain V-II region NIG-58 Tacrolimus Ig lambda chain V-VI region SUT ITPR1 Ig heavy chain V-I region Mot IGKV4-1Ig kappa chain V-I region CAR IKBKB Ig heavy chain V-III region LAY SOS1 IGLVIg kappa chain V-III region HAH PSME1 Ig lambda chain V-VI region EB4 Ig kappa chain V-II region GM607 IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region OU Ig heavy chain V-I region EU Ig heavy chain V-II region SESS PPP3R1 Ig kappa chain V-IV region Len Ig heavy chain V-I region SIE p-4Y-PIK3AP1 ATPIGLC7Ig kappa chain V-III region VH GRB2-1 BCAP Signalosomep-6Y-SYK Ig kappa chain V-III region Ti Ig kappa chain V-I region Kue Ig heavy chain V-I region ND Ig kappa chain V-I region Ni PSMB4 Ig kappa chain V-IV region Len BCRIg heavy chain V-II region SESS PSMB3 Ig lambda chain V-IV region MOL PSMD10 Ig kappa chain V-I region AG PSMB10 IKKAIKKBNEMOIg kappa chain V-I region HK101 RasGRP1/3Ig kappa chain V-I region Mev Ig heavy chain V-II region OU IGHDIg lambda chain V-VI region NIG-48 Ig heavy chain V-II region NEWM Ig heavy chain V-III region WAS Ig lambda chain V-II region MGC PIIg kappa chain V-I region HK101 Ig lambda chain V-IV region Kern Ig kappa chain V-IV region STH Ig lambda chain V-I region EPS IGLC3Ig lambda chain V-II region NIG-58 Ig heavy chain V-III region JON IGHVIg heavy chain V-III region BUT REL Ig heavy chain V-II region SESS Ig heavy chain V-II region DAW Ig kappa chain V-I region HK101 STIM1TRPC1IGKV4-1Ig heavy chain V-II region COR Ig heavy chain V-II region HE Ig heavy chain V-I region EU Ig kappa chain V-II region GM607 Ig kappa chain V-I region WEA Ig kappa chain V-I region EU PPP3R1 Ig kappa chain V-I region Hau Ig heavy chain V-III region GAL IGHV7-81Ig heavy chain V-II region ARH-77 p-S157,S161-NFKBIE Ig heavy chain V-I region WOL Ig lambda chain V-II region NIG-58 Ig lambda chain V-II region BO p-6Y-SYK Ig lambda chain V-I region WAH Phosphorylated NFATC1/2/3Ig kappa chain V-III region HAH Ig lambda chain V-IV region Kern Ig heavy chain V-III region TEI Ig heavy chain V-III region BRO Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-I region HA IGKCPPIA Ig heavy chain V-II region MCE GRB2-1 Ig heavy chain V-I region EU Ca2+Phosphatidylserine IGLC6Ig kappa chain V-I region Lay Ig kappa chain V-II region RPMI 6410 IGHVIg kappa chain V-I region OU IGLC7SKP1 Ig kappa chain V region EV15 Ig kappa chain V-IV region Len p-RasGRP1,3DAGIg heavy chain V-I region WOL Ig lambda chain V-VI region EB4 Ig lambda chain V-II region MGC ADPIGHV7-81IGLC3NFKB1Ig kappa chain V-I region Ka KRASIg lambda chain V-I region NEW Ig kappa chain V-I region Hau Ig kappa chain V-I region WAT Ig heavy chain V-III region LAY p-S559,S644,S652-CARD11Ig kappa chain V-I region BAN Ig lambda chain V-VI region NIG-48 IGHDIgH heavy chain V-III region VH26 precursor PSMD11 Ig kappa chain V-I region Rei Ig lambda chain V-I region WAH Ig heavy chain V-III region LAY CUL1 STIM1CalciumIg heavy chain V-III region GA Ig heavy chain V-III region ZAP Ig heavy chain V-II region OU IGLC7NFKB1ITPR2 Ig lambda chain V-I region BL2 PSMC3 Ig lambda chain V-VI region NIG-48 Ig lambda chain V-IV region Kern Ig heavy chain V-II region MCE PSMB7 Ig lambda chain V-VII region MOT DAGIg lambda chain V-III region LOI Ig heavy chain V-III region JON FKBP1ATacrolimusIg kappa chain V-I region CAR p21 RASGDPIg kappa chain V-I region Ni PIADPIg heavy chain V-III region TIL Ig kappa chain V-I region AG Ig lambda chain V-IV region Kern Ig heavy chain V-III region BRO Ig kappa chain V-III region WOL TRPC1Ig lambda chain V-VI region NIG-48 DAG Ig lambda chain V-VI region NIG-48 Ig lambda chain V-II region BOH Ig lambda chain V-III region LOI IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Lay Ig heavy chain V-II region HE BLNK Ig kappa chain V-I region Gal Ig kappa chain V-III region POM Ig heavy chain V-III region TRO BTKIg kappa chain V-I region Scw BTRC Ig kappa chain V-III region Ti Ig kappa chain V-I region Ni Ig lambda chain V-II region NEI IGLVIg lambda chain V-VII region MOT Ig kappa chain V-II region MIL Ig kappa chain V-I region EU Ig kappa chain V-I region Roy Ig lambda chain V-II region BO ORAI1 Ig kappa chain V-I region Ka MALT1 Ig heavy chain V-I region SIE PSMB11 Ig kappa chain V-III region B6 Ig kappa chain V-I region Hau Ig kappa chain V-II region GM607 Ig heavy chain V-III region LAY IGLVIg heavy chain V-II region SESS Ig heavy chain V-III region TUR VAV1Ig kappa chain V-I region AU Ub-21,22-p-S32,S36-NFKBIA Ig lambda chain V-II region VIL Ig lambda chain V-III region SH Ig kappa chain V-I region HK101 Ig lambda chain V-VII region MOT Ig kappa chain V-III region CLL Ig heavy chain V-I region WOL p-Y188,Y199-CD79A Ig heavy chain V-III region GAL Ig lambda chain V-I region NEWM IGLC1Ig kappa chain V-I region CAR IGKCIg heavy chain V-III region KOL Ig kappa chain V-I region Gal IGLC2Ig heavy chain V-III region DOB Ig heavy chain V-II region OU Ig lambda chain V-VI region AR IGHDIg kappa chain V-I region WEA Ig kappa chain V-I region Hau Ig kappa chain V-I region Wes Ig lambda chain V-I region WAH Ig kappa chain V-III region SIE IGKV4-1PIK3CDPIK3R1Ig lambda chain V-VI region SUT IGHMIg kappa chain V-III region HIC Ig lambda chain V-II region WIN Ig heavy chain V-III region NIE MALT1 Ig lambda chain V-II region WIN p-Y771,Y783-PLCG1 Ig heavy chain V-II region WAH p-5Y-BLNK IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Daudi Ig lambda chain V-VI region AR Ig lambda chain V-I region MEM Ig kappa chain V-I region Roy Ig lambda chain V-IV region Bau Ig kappa chain V-I region Ni Ig heavy chain V-II region SESS Ig kappa chain V-I region DEE Ig heavy chain V-III region WEA Ig kappa chain V-III region CLL Ig lambda chain V-II region TRO p-Y194,Y195,Y272-SHC1-1Ig heavy chain V-I region WOL Ig heavy chain V-II region SESS RELA Ig kappa chain V-I region Lay IKBKG REL Ig kappa chain V-I region HK101 Ig heavy chain V-II region NEWM IGLC6Ig kappa chain V-III region CLL Ig kappa chain V-II region TEW Ig lambda chain V-I region NEWM p-Y196,Y207-CD79B Ig heavy chain V-III region HIL Ig kappa chain V-III region NG9 Ig heavy chain V-III region GA p-Y196,Y207-CD79B Ig lambda chain V-I region VOR Ig kappa chain V-III region VH Ig lambda chain V-II region MGC PSMD3 PPP3CA Ig heavy chain V-III region JON PSMD13 Ig heavy chain V-III region TEI Ig lambda chain V-II region TOG STIM1 Orai1 dimerIg lambda chain V-IV region Bau Ig heavy chain V-III region DOB IGHVIg lambda chain V-I region HA Ig heavy chain V-III region DOB ORAI1 Ca2+ Ig kappa chain V-III region B6 IP3 receptorIP3 complexPSMD2 PIIg kappa chain V-I region Rei Ig heavy chain V-III region BUR Ig lambda chain V-IV region X Ig kappa chain V-III region VG Ig heavy chain V-I region HG3 Ig kappa chain V-I region BAN Ig lambda chain V-VI region SUT IGKCCa2+IGLC3Ig kappa chain V-III region GOL ITPR1 NFKB1Ig lambda chain V-VI region EB4 Ig kappa chain V-I region Rei Ig heavy chain V-III region NIE SH3KBP1 Ig kappa chain V-I region Ni Ig heavy chain V-III region CAM Ig lambda chain V-I region NEW Ig kappa chain V-I region AG Ig heavy chain V-III region TRO Ig kappa chain V-I region CAR Ig heavy chain V-III region BUT Ig heavy chain V-II region WAH Ig lambda chain V-III region SH Ig heavy chain V-II region OU Ig heavy chain V-III region KOL Ig kappa chain V-III region NG9 Ig lambda chain V-II region NIG-58 Ig heavy chain V-III region TUR IGLC7ITPR3 Ig lambda chain V-II region TRO IGLC7Ig kappa chain V-III region B6 Ig heavy chain V-III region TIL IGHVIg kappa chain V-II region Cum PSMB5 Ig lambda chain V-VI region SUT Ig kappa chain V-I region Rei PPP3CA Ig kappa chain V-I region Bi Ig kappa chain V-III region Ti IGHVIg lambda chain V-II region VIL Ig heavy chain V-III region LAY Ig kappa chain V-I region Hau Ig kappa chain V-I region Lay Ig kappa chain V-I region AU PIK3CD PSMA5 Antigenp-BCRSYKIg heavy chain V-I region Mot Ig lambda chain V-VI region WLT IGKVA18Ig heavy chain V-III region GA Ig heavy chain V-III region HIL Ig kappa chain V-II region MIL Ig heavy chain V-III region GA Ig kappa chain V region EV15 IGKV4-1Ig heavy chain V-I region HG3 Ig kappa chain V region EV15 NFKBIE Ig kappa chain V-II region MIL Ig kappa chain V-I region Scw Ig heavy chain V-II region ARH-77 Ig heavy chain V-II region COR Ig heavy chain V-III region HIL p-Y196,Y207-CD79B p-CARMA1 OligomerIg lambda chain V-II region VIL IGLC1IGKVA18Ig kappa chain V-I region WAT Ig lambda chain V-II region NEI IKBKG Ig heavy chain V-II region WAH Ig lambda chain V-I region VOR Ig kappa chain V-IV region JI Ig lambda chain V-II region NEI Ig kappa chain V-I region Ka Ig kappa chain V-I region Daudi Ig lambda chain V-IV region Bau Ig lambda chain V-VI region EB4 SCF-beta-TrCp1/2Ig kappa chain V-I region OU Ig lambda chain V-I region VOR Ig lambda chain V-VI region SUT Ig lambda chain V-II region TRO Ig kappa chain V-II region Cum Ig heavy chain V-III region WEA p-Y139-DAPP1 PSME2 Ig heavy chain V-III region BRO p-S32,S36-NFKBIA GRB2-1 Ig kappa chain V-I region Gal Ig lambda chain V-IV region Hil Ig heavy chain V-III region TIL Ig heavy chain V-II region MCE Ig kappa chain V-III region IARC/BL41 Ig lambda chain V-I region NIG-64 Ig lambda chain V-VII region MOT Ig kappa chain V-III region Ti IIg lambda chain V-IV region Hil Ig heavy chain V-II region COR Ig heavy chain V-III region TUR Active CalmodulinIGKV4-1ATPCa2+ SKP1 Ig kappa chain V-III region VH Ig heavy chain V-III region ZAP GRB2-1 p-S19,S23-NFKBIB Ig kappa chain V-I region Ka CHUK Ig heavy chain V-II region WAH VAV1 Ig kappa chain V-III region VH Ig kappa chain V-I region Mev Ig heavy chain V-III region CAM Ig kappa chain V-IV region STH CD19 SignalosomeHRASPSMB6 IGHMIg lambda chain V-VI region AR Ig kappa chain V-II region Cum Ig kappa chain V-I region Kue Ig lambda chain V-III region LOI Ig heavy chain V-II region WAH Ig kappa chain V-III region POM Ig lambda chain V-I region BL2 Ig kappa chain V-III region GOL Ig kappa chain V-I region BAN Ig kappa chain V-I region AG Ig heavy chain V-II region DAW IGHMIg heavy chain V-III region TEI Ig heavy chain V-II region NEWM Ig kappa chain V-IV region B17 Ig lambda chain V-II region BO Ig kappa chain V-III region CLL Ig kappa chain V-I region Lay IGLC2Ig lambda chain V-I region EPS Ig heavy chain V-III region ZAP PSMD7Ig kappa chain V-I region Rei Ig heavy chain V-III region GA Ig kappa chain V-IV region STH Ig kappa chain V-I region BAN IGLC2Ig lambda chain V-IV region MOL Ig kappa chain V-IV region STH Ig heavy chain V-III region WEA Ig kappa chain V-I region Wes IKBKB Ig lambda chain V-VI region NIG-48 p-Y188,Y199-CD79A Calcineurin NFKB1Ig kappa chain V-III region HAH SOS1 Ig kappa chain V-III region NG9 Ig heavy chain V-II region NEWM Ig kappa chain V-III region GOL Ig kappa chain V-III region HIC Ig kappa chain V-III region POM PSMD5 PSMC4 Ig kappa chain V-I region Hau Ig kappa chain V-I region Walker PIK3CD Ig lambda chain V-IV region MOL PSMA2 Ig lambda chain V-III region LOI IGLC1Ig kappa chain V-III region HIC PIIg kappa chain V-III region VH Ig lambda chain V-II region WIN Ig heavy chain V-III region TEI p-14S-NFATC2 Ig lambda chain V-V region DEL p-Y239,Y240,Y317-SHC1-2 Ig kappa chain V-III region VG Ig heavy chain V-III region BUR Ig lambda chain V-I region NEWM Ig kappa chain V-III region POM Ig heavy chain V-II region ARH-77 ITPR2 Ig kappa chain V-IV region JI Ig lambda chain V-I region MEM Ig kappa chain V-III region HAH IGLC1IGKV1-5Ca2+ MALT1 Ig heavy chain V-I region Mot Ig heavy chain V-III region POM Ig lambda chain V-IV region X PSMD9 CD79B Ig heavy chain V-III region BUR PIP3 activates AKT signalingIg heavy chain V-III region JON Ig lambda chain V-II region BO Ig lambda chain V-VI region AR Ig heavy chain V-III region GA IGLC1Ig lambda chain V-II region BOH Ig kappa chain V-I region AU Ig kappa chain V-II region GM607 Ig lambda chain V-II region BOH STIM1 Ig heavy chain V-III region TRO IGHDIg kappa chain V-I region Walker IGKVA18Ig lambda chain V-II region NEI Ig kappa chain V-III region VH Ig lambda chain V-IV region Kern IKBKG CARD11Ig lambda chain V-I region MEM Ig lambda chain V-I region NEW Ig kappa chain V-III region Ti PSMD4Ig kappa chain V-IV region STH Ig lambda chain V-IV region Hil Ig kappa chain V-I region Daudi Ig lambda chain V-I region BL2 Ig kappa chain V-IV region Len Ig heavy chain V-I region HG3 Ig kappa chain V-I region Roy Ig kappa chain V-I region Ka Ig lambda chain V-I region EPS p-BCL10 Ig kappa chain V-III region HAH Ig heavy chain V-III region BRO Ig kappa chain V-IV region STH Ig kappa chain V-II region TEW Ig kappa chain V-I region Kue Ig heavy chain V-III region TRO Ig heavy chain V-II region SESS IGLVIg lambda chain V-IV region Bau Ig lambda chain V-I region EPS IGLC6Ig kappa chain V-II region Cum Ig heavy chain V-III region WEA Ig lambda chain V-II region TOG IGHVIg kappa chain V-I region WEA Ig kappa chain V-III region IARC/BL41 PSMD8 CARMA1MALT1BCL10Zn2+ Ig lambda chain V-I region WAH Ig kappa chain V-IV region Len Ig heavy chain V-III region GAL Ig lambda chain V-II region NIG-84 STIM1 Ig kappa chain V-II region TEW Ig heavy chain V-III region CAM Ig heavy chain V-III region DOB FBXW11 RELA Ig lambda chain V-I region NEW Ig lambda chain V region 4A RELA Ig kappa chain V-II region FR Ig heavy chain V-III region TUR Ig heavy chain V-II region HE Ig kappa chain V-I region Rei IGLC6Ig lambda chain V-I region NEW Ig heavy chain V-I region ND Ig kappa chain V-I region CAR Ig kappa chain V-III region HIC Ig kappa chain V-III region SIE Ig heavy chain V-III region TIL Ig kappa chain V-I region DEE Ig kappa chain V-I region Walker Ig lambda chain V-IV region Hil Ig kappa chain V-I region Walker Ig lambda chain V-I region BL2 Ig kappa chain V-II region FR Ig lambda chain V-II region TOG Ig kappa chain V-I region WEA Ig lambda chain V-II region NIG-84 CBL IGKCPRKCBIGHV7-81Ig kappa chain V-I region WAT Ig kappa chain V-I region BAN Ig lambda chain V-I region HA Ig heavy chain V-III region NIE Ig lambda chain V-I region NEWM Ig kappa chain V-I region Bi Ig kappa chain V-II region MIL Ig lambda chain V region 4A Ig kappa chain V region EV15 Ig lambda chain V region 4A Ig lambda chain V-V region DEL Ig heavy chain V-II region DAW ADPIg kappa chain V-IV region B17 Ig heavy chain V-III region BUT Ig lambda chain V-VI region EB4 Ig heavy chain V-III region CAM Ig heavy chain V-I region SIE p-Y753,Y759,Y1217-PLCG2 Ig kappa chain V-I region Wes BLKIg lambda chain V-I region WAH Ig kappa chain V-I region AU Ig kappa chain V-III region HIC Ig lambda chain V-II region MGC Ig heavy chain V-III region KOL Ig heavy chain V-III region BRO Ig heavy chain V-I region ND Cyclosporin A IGKV1-5Ig heavy chain V-III region POM Ig heavy chain V-III region CAM IGKV4-1Ig kappa chain V-I region DEE Ig kappa chain V-II region TEW Ig kappa chain V-III region WOL Ig kappa chain V-I region WAT STIM1 DimerPSMC6Ig heavy chain V-III region TIL CD79B CHUK Ig heavy chain V-II region ARH-77 IGLC2Ig kappa chain V-III region VG IGLC1Ig kappa chain V-II region Cum Ig kappa chain V-I region AG Ig lambda chain V-II region WIN Ig kappa chain V-I region EU Ig kappa chain V-III region NG9 p-S559,S644,S652-CARD1137, 38, 4967144669267, 976629, 105, 107, 1436440, 6247, 66, 74, 106, 1351291784123, 13912733, 47, 106, 13549149361202558, 79, 130, 140


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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).

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  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
  61. Uckun FM, Burkhardt AL, Jarvis L, Jun X, Stealey B, Dibirdik I, Myers DE, Tuel-Ahlgren L, Bolen JB.; ''Signal transduction through the CD19 receptor during discrete developmental stages of human B-cell ontogeny.''; PubMed Europe PMC Scholia
  62. Shinohara H, Kurosaki T.; ''Comprehending the complex connection between PKCbeta, TAK1, and IKK in BCR signaling.''; PubMed Europe PMC Scholia
  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
  84. Garcia-Cozar FJ, Okamura H, Aramburu JF, Shaw KT, Pelletier L, Showalter R, Villafranca E, Rao A.; ''Two-site interaction of nuclear factor of activated T cells with activated calcineurin.''; PubMed Europe PMC Scholia
  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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  96. Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF.; ''STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels.''; PubMed Europe PMC Scholia
  97. Fu C, Turck CW, Kurosaki T, Chan AC.; ''BLNK: a central linker protein in B cell activation.''; PubMed Europe PMC Scholia
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  102. Tanner MJ, Hanel W, Gaffen SL, Lin X.; ''CARMA1 coiled-coil domain is involved in the oligomerization and subcellular localization of CARMA1 and is required for T cell receptor-induced NF-kappaB activation.''; PubMed Europe PMC Scholia
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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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