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

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5-7, 13, 22...41, 64, 112, 143, 16124, 61, 81, 107, 108, 1693, 63, 14731, 32, 62, 125, 13768, 77, 80, 90, 126...16, 33, 53, 54, 103...4, 5, 30, 35, 43...51, 58, 93, 95, 14439, 92, 120, 139102, 123, 1259, 132, 1401, 10, 27, 34, 50...1237, 23, 122, 12749, 59, 74, 110, 122...15, 36, 52, 78, 13579, 136, 15958, 87, 113, 129, 133...16, 33, 53, 54, 103...60, 67, 70, 16615, 52, 13512, 42, 1168, 97, 105, 106, 124...6, 22, 40, 45, 49...14, 94, 104, 114, 11732, 62, 12318, 65, 75, 84, 8556, 140, 151, 1564, 30, 35, 11126, 56, 97, 99, 105...47, 79, 136, 15948, 66, 115, 1212, 89, 160, 17071, 117, 119, 128, 1547, 23, 44, 69, 82...6615524endoplasmic reticulum lumencytosolnucleoplasmplasma membranep-S32,S36-NFKBIA Ig heavy chain V-II region OU p-6Y-CD19 IGKV2D-30 Antigen:BCRIg lambda chain V region 4A PSMA5 IGKV1-5(23-?) IGLC3 Ig heavy chain V-III region BRO SHFM1 IGLV(23-?) Ig heavy chain V-III region JON IGLC6 Ig kappa chain V-I region Wes Ig kappa chain V-II region RPMI 6410 S-Farn-Me KRAS4B RASGRP1,3Ig heavy chain V-II region MCE Ig kappa chain V-II region FR Ig heavy chain V-III region JON ITPR3 Ig heavy chain V-III region TRO IgH heavy chain V-III region VH26 precursor IGHD DephosphorylatedNFATC1,2,3IGKVA18(21-?) IGLV(23-?) Ig kappa chain V-I region HK101 PSIg lambda chain V-I region HA p-6Y-CD19 PSMD9 Ig kappa chain V-I region DEE Ig lambda chain V-I region HA Ig lambda chain V-I region NEWM Ig kappa chain V-I region Daudi PI(3,4,5)P3 IKBKG IGHV1-2 Ig lambda chain V-IV region Kern Ig kappa chain V-II region Cum Cyclosporin A Ig heavy chain V-III region JON Ig kappa chain V-III region B6 IGKV4-1(21-?) Ig heavy chain V-III region WEA Ig kappa chain V-II region FR Ig lambda chain V-II region NEI Ca2+ ADPGTPGRB2-1 Ig lambda chain V-VI region AR IgH heavy chain V-III region VH26 precursor p-4Y-PIK3AP1 IGLC3 Antigen Ig lambda chain V-III region LOI p-Y196,Y207-CD79B NFKB1(1-433) IGKV2D-30 IGKV2D-30 Ig heavy chain V-III region DOB Ig kappa chain V-I region Gal Ig kappa chain V-III region POM IgH heavy chain V-III region VH26 precursor Ig heavy chain V-III region BRO Ig kappa chain V-I region Wes Ig kappa chain V-III region POM IGKVA18(21-?) IGHV1-2 Ig heavy chain V-II region NEWM IgH heavy chain V-III region VH26 precursor Ig heavy chain V-III region CAM Ig lambda chain V-IV region Bau IGLC7 STIM1 Ig lambda chain V-IV region Hil Ig lambda chain V-VI region AR Ig heavy chain V-I region HG3 MyrG2-PalmC3,6-FYN PSMB9 IGHM IGKV2D-30 Ig kappa chain V-I region AG IGHV1-2 Ig lambda chain V-VI region AR VAV1Ig heavy chain V-I region EU PSMD5 PSMD10 Ig lambda chain V-II region TOG Ig heavy chain V-II region OU Ig lambda chain V-IV region Hil Ig lambda chain V-I region NEWM IGLC6 Ig kappa chain V-I region HK101 Ig kappa chain V-I region Gal Ig kappa chain V-I region Wes ADPIGLC3 Ig kappa chain V-I region AG Ig heavy chain V-II region NEWM p-BCL10 Ig kappa chain V region EV15 Ig kappa chain V-I region Wes IGLC1 Ig lambda chain V-II region MGC Ig heavy chain V-III region BRO REL Ig kappa chain V-I region AG Ig lambda chain V-I region HA Ig heavy chain V-II region OU IGKV4-1(21-?) Ig kappa chain V-III region B6 Ig kappa chain V region EV15 Ig heavy chain V-III region BUT MAP3K7 Ig lambda chain V-I region NEW IGHV(1-?) Ig heavy chain V-II region ARH-77 IGKC ATPp-Y188,Y199-CD79A Antigen Ig kappa chain V-III region POM GRB2-1 UBC(609-684) IGKV1-5(23-?) Ig kappa chain V-I region DEE Ig kappa chain V-II region FR GTP IGKV1-5(23-?) Ig heavy chain V-III region JON Ig lambda chain V-IV region Hil p-T133-RASGRP3 Ig heavy chain V-I region EU ATPGDPp-Y762,807,822-CD22 Ig kappa chain V-I region HK101 PSME2 IGKV4-1(21-?) IGKV3D-20 IGKVA18(21-?) CD22Ig lambda chain V-II region NEI PLCG2 Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y223,Y551-BTK:NCK1:VAV1:PLCG2ORAI1 Ig lambda chain V-I region NEW IGLC3 Ig lambda chain V-I region NEW PSMB8 ATPIg heavy chain V-II region OU S-Farn-Me-PalmS KRAS4A Ca2+Ig kappa chain V-II region FR Ig heavy chain V-III region TRO Ig lambda chain V-II region TOG ORAI dimerIgH heavy chain V-III region VH26 precursor IGHM Ig kappa chain V-III region VG Ig lambda chain V-I region HA BLNK IGLC7 Ig heavy chain V-III region TRO Ig kappa chain V-I region AU Ig lambda chain V-I region VOR IGLC1 IgH heavy chain V-III region VH26 precursor Ig heavy chain V-II region MCE IGKV3D-20 Ig heavy chain V-III region TRO RELA IGKV2-28 IGKV2D-30 IGLV(23-?) UBC(381-456) NFKB1(1-433) ITPR2 Ig kappa chain V-III region VG PPIA Ig heavy chain V-III region DOB Ig heavy chain V-III region BUT Ig lambda chain V-IV region Bau IKBKB SKP1 IGKV1-5(23-?) FKBP1A:TacrolimusIGLC2 Ig heavy chain V-III region CAM Ig heavy chain V-II region MCE IGKV3D-20 IGLC1 Ig kappa chain V-I region Gal Ig kappa chain V-I region AG Ig kappa chain V-I region BAN Ig heavy chain V-III region WEA Ig kappa chain V-I region AU p-S177,S181-IKBKB Ig lambda chain V-I region NEW Ig heavy chain V-II region NEWM SOS1 p-CARMA1:MALT1:p-BCL10PSMD2 CRAC channelIg heavy chain V-I region HG3 p-S559,S644,S652-CARD11 NF-kappaBp50,p65,c-Rel:ub-p-IKBp-Y223,Y551-BTK Ig kappa chain V-III region POM GRB2-1 p-Y188,Y199-CD79A Ig lambda chain V-IV region Hil Ig lambda chain V-IV region Hil Ig heavy chain V-III region DOB Ig heavy chain V-III region KOL Ig heavy chain V-III region CAM Ig heavy chain V-III region WEA Ig kappa chain V-II region Cum PPP3R1 Ig kappa chain V region EV15 IGLV(23-?) AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerORAI2 Ig lambda chain V-I region VOR p-S157,S161-NFKBIE IGHV(1-?) Ig heavy chain V-III region TRO Ig kappa chain V-I region BAN IGHM IKBKB IGKV1-5(23-?) PIK3R1 CD19 IGHD PSMF1 IGHV7-81(1-?) Ig lambda chain V-II region TOG Ig kappa chain V-I region Gal Ig heavy chain V-II region ARH-77 IGLC6 Ig lambda chain V-II region BOH Ig kappa chain V-I region DEE p-S19,S23-NFKBIB S-Farn-Me-PalmS KRAS4A NCK1 Ig kappa chain V-I region Gal IGHD GRB2-1 IGHM IGHD Ig lambda chain V-I region VOR IGKV1-12 IGKV3D-20 IGLC1 IGLC1 IGKV4-1(21-?) ATPIg lambda chain V-III region SH Ig kappa chain V-I region Wes Ig kappa chain V-II region Cum NCK1 Ig heavy chain V-III region DOB IGKC Ig heavy chain V-III region KOL p-Y762,807,822-CD22 IGKV1-5(23-?) Ig heavy chain V-III region JON Ig lambda chain V-I region NEWM Ig kappa chain V-III region VG IGKVA18(21-?) GRB2-1Antigen CD19 Signalosomep-Y196,Y207-CD79B Ig heavy chain V-III region JON Ig lambda chain V-I region VOR VAV1 PSMC5 Ig kappa chain V-I region Daudi Ig heavy chain V-II region OU BTKIGLC3 CHUK CD79B IGLV(23-?) Ig kappa chain V-I region BAN Calcineurin (CaN)IGHV1-2 ORAI1 Ig kappa chain V-I region Gal Ig heavy chain V-I region EU Ig kappa chain V-I region AG Ig heavy chain V-III region BUT PSMA3 IGLC1 IGKV2-28 IGLC3 Ig kappa chain V region EV15 Ig lambda chain V-II region MGC Ig heavy chain V-III region BUT Ig lambda chain V-IV region Hil Ig kappa chain V-II region RPMI 6410 IGKV1-12 Ig heavy chain V-II region ARH-77 Ig lambda chain V-II region BOH ATPIGKVA18(21-?) IGLC2 Ig lambda chain V-I region HA IGKV2D-30 PIK3R1 IGHV1-2 IGLC2 Ig lambda chain V-III region LOI PI(3,4,5)P3 Ig heavy chain V-III region JON Ig kappa chain V-III region VG Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-III region CAM Ig lambda chain V-III region SH p-S19,S23-Ub-NFKBIB p-Y139-DAPP1:PIP3Ig kappa chain V-III region VG IGHV(1-?) IGKC IGKV3D-20 AntigenAntigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1Ig kappa chain V-I region AU Ig kappa chain V-I region DEE Ig lambda chain V-IV region Hil BLNK:GRB2:SOS1:CIN85DAPP1Ig kappa chain V-I region Daudi Ig heavy chain V-I region EU Ig heavy chain V-III region JON Ig lambda chain V-II region MGC IGKV2-28 Ig heavy chain V-II region NEWM IGLC1 p-S157,S161-Ub-NFKBIE Ig lambda chain V-IV region Bau p-Y196,Y207-CD79B ITPR1 AHCYL1 Ig kappa chain V-II region Cum Ig kappa chain V-I region HK101 IGLV(23-?) Ig lambda chain V-III region SH p-S559,S644,S652-CARD11 CALM1IGLC6 REL IGKV1-12 Ig kappa chain V-III region POM p-Y139-DAPP1 Ig kappa chain V-II region FR p-S32,S36-NFKBIA Ig lambda chain V-I region HA IGKV2D-30 Ig heavy chain V-II region MCE IGLC3 Ig kappa chain V-III region B6 Ig lambda chain V-II region NEI Ig heavy chain V-II region WAH Ig heavy chain V-III region JON Ig lambda chain V-I region VOR Ig heavy chain V-I region EU Ig lambda chain V-III region SH Ig kappa chain V-I region Daudi Ig lambda chain V-II region TOG Ig heavy chain V-III region KOL Ig kappa chain V-III region B6 Ig heavy chain V-III region TRO Ig kappa chain V-III region VG RELA FKBP1A IGHV7-81(1-?) Ig heavy chain V-III region TRO Ig lambda chain V-II region BOH PSMA4 IGHM p-Y188,Y199-CD79A IGKV3D-20 Ig lambda chain V region 4A IGHD Ig lambda chain V-II region BOH TRPC1 IGLC1 Ig lambda chain V region 4A PSME4 IGKV1-12 PSMD7 PI(3,4,5)P3 Ig lambda chain V-II region NEI Ig kappa chain V-II region FR Ig heavy chain V-III region BUT Ig heavy chain V-II region NEWM PSMC6 p-4Y-PIK3AP1Ig kappa chain V-III region VG Ig kappa chain V-I region BAN Ig lambda chain V region 4A Ig lambda chain V-II region TOG IgH heavy chain V-III region VH26 precursor Ig heavy chain V-III region JON p-Y188,Y199-CD79A IGKVA18(21-?) Ig lambda chain V-III region LOI Ig heavy chain V-II region NEWM IGKC Ig kappa chain V region EV15 IGKVA18(21-?) BTRC Ig heavy chain V-III region KOL Ig kappa chain V-II region FR Ig kappa chain V-I region BAN Ig lambda chain V-II region MGC Antigen Ig kappa chain V-I region Gal IGLC6 Antigen IGHV(1-?) Ig lambda chain V region 4A IGKV4-1(21-?) PPP3CA Ig kappa chain V region EV15 Ig heavy chain V-III region TRO Ig heavy chain V-I region HG3 Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-I region NEW ADPPPP3CB ITPR1 IGKV1-12 PSMA6 IGHM IGHV7-81(1-?) Ca2+Ig lambda chain V-I region HA Ig lambda chain V-II region MGC SH3KBP1 IGHM Ig lambda chain V-II region TOG Ig heavy chain V-II region NEWM p-Y196,Y207-CD79B Ig lambda chain V-IV region Kern p-S19,S23-NFKBIB MyrG2-BLK p-5Y-BLNK Ig lambda chain V-VI region AR LYN, p-SYKIGLC2 (BTRC:CUL1:SKP1),(FBXW11:CUL1:SKP1)Ig lambda chain V-II region TOG Antigen Ig lambda chain V-II region NEI Ig kappa chain V region EV15 PI(3,4,5)P3p21 RAS:GTPIg kappa chain V-I region DEE p-BCL10Ig lambda chain V-I region NEW ADPIg kappa chain V region EV15 IGLC7 Ig heavy chain V-III region WEA Ig heavy chain V-II region OU PSMB4 Ig lambda chain V region 4A Antigen IGHV7-81(1-?) IGLC2 Ig lambda chain V region 4A Ig heavy chain V-II region MCE IGLV(23-?) Ig kappa chain V-III region VG NFKB1(1-433) IGKC IGKV2D-30 Ig kappa chain V-I region AU Ig heavy chain V-II region WAH Ig kappa chain V-II region Cum Ig kappa chain V-II region FR NCK1Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y551-BTK:NCK1:VAV1:PLCG2IGKV1-12 PSMD4 Ig heavy chain V-II region OU IGKV2D-30 Ig lambda chain V-IV region Bau Ig kappa chain V-I region AU Ig lambda chain V-I region NEW Ig heavy chain V-III region CAM VAV1 Ig heavy chain V-III region WEA IGLC2 Ig heavy chain V-III region CAM IGHD Ig lambda chain V-IV region Kern Antigen IGLC2 p-5Y-BLNK Ig kappa chain V-I region Gal Ig heavy chain V-III region WEA Ig kappa chain V-I region DEE Ig heavy chain V-II region OU Ig heavy chain V-III region DOB Antigen Ig kappa chain V-II region FR Ig kappa chain V-III region B6 Ig heavy chain V-II region NEWM ATPIGLC1 IGLV(23-?) S-Farn-Me PalmS NRAS Ig heavy chain V-II region ARH-77 Ig lambda chain V-VI region AR IGKVA18(21-?) IGKV1-5(23-?) IGLC6 Ig heavy chain V-III region CAM Ig heavy chain V-III region KOL Ig heavy chain V-III region BRO ITPR3 Ig lambda chain V-IV region Hil Ig heavy chain V-III region KOL Ig kappa chain V-I region DEE DAG Ig heavy chain V-III region DOB IGLC7 Ig kappa chain V-I region AG IGKC Ig heavy chain V-II region MCE IGKV1-5(23-?) IGHD SH3KBP1 PSMD11 IGKV2-28 Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-II region BOH IGLV(23-?) Ig kappa chain V region EV15 Ig lambda chain V-IV region Bau IGKV1-5(23-?) Ig kappa chain V-I region Wes p-Y188,Y199-CD79A Ig kappa chain V-I region DEE Ig heavy chain V-III region BRO p-Y188,Y199-CD79A Ig lambda chain V region 4A Ig heavy chain V-III region KOL Ig heavy chain V-III region BRO Ig lambda chain V-II region MGC Ig heavy chain V-I region HG3 Ig lambda chain V-IV region Hil IGKV2-28 Ig kappa chain V-I region AU Ig heavy chain V-II region OU Ig lambda chain V-III region LOI PSMB10 p-Y196,Y207-CD79B Ig kappa chain V-II region Cum RELA ADPIg heavy chain V-III region CAM p-CARMA1:MALT1:p-BCL10:TAK1:IKKIg kappa chain V-I region AU Ig kappa chain V-III region VG Ig heavy chain V-II region ARH-77 Ig heavy chain V-II region MCE Ig lambda chain V-IV region Bau Ig kappa chain V-I region Gal Ig lambda chain V-II region NEI p-Y753,Y759,Y1217-PLCG2 IGKC Ig lambda chain V-III region SH Ig lambda chain V-III region LOI PI(3,4,5)P3 p-5Y-BLNK Ig heavy chain V-II region MCE Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-III region BUT Ig kappa chain V-I region Daudi IGLV(23-?) Ig kappa chain V-I region Gal IGKC NFKB1(1-433) IGLC7 Ig kappa chain V-III region VG p-Y196,Y207-CD79B ADPActivated PKC betaIg heavy chain V-II region MCE NFKB1(1-433) Ca2+ UBB(77-152) Ig kappa chain V-III region POM Ig lambda chain V-I region NEWM IGKV2-28 Ig kappa chain V region EV15 MyrG2-PalmC3-LYNIg heavy chain V-I region HG3 ATPIGLC7 PSME1 Ig heavy chain V-II region NEWM PLCG2 Ig lambda chain V-VI region AR Ig kappa chain V-I region HK101 IGLC3 Ig lambda chain V-III region SH p-13S-NFATC3 Ig kappa chain V-I region BAN IGKVA18(21-?) IGLC3 UBC(153-228) Ig kappa chain V-I region AU NCK1 Ig heavy chain V-III region BUT PIK3CD ITPR2 SYKIg kappa chain V-I region DEE IGHD Ig kappa chain V-I region AU Ig lambda chain V-IV region Kern p-S257-NFATC1 Ig heavy chain V-II region NEWM PIK3CD:PIK3R1Ig kappa chain V-III region B6 Ig kappa chain V-III region POM IGKV1-12 Ig lambda chain V-II region MGC BTK Ig kappa chain V-I region Daudi Ig heavy chain V-III region TRO PLCG2 IGKV1-12 Ig heavy chain V-II region MCE Ig lambda chain V-IV region Hil Ig kappa chain V-I region Daudi IGKV3D-20 Ig heavy chain V-III region TRO ADPIGHV7-81(1-?) Ig kappa chain V-II region Cum p-S265-NFATC3 IGLC3 Ig lambda chain V region 4A Ig lambda chain V-VI region AR UBC(305-380) Ig kappa chain V-I region AU ATPPSMC4 Ig heavy chain V-III region WEA PSMD1 Ig kappa chain V-I region AG IgH heavy chain V-III region VH26 precursor IGHV(1-?) Ig lambda chain V-IV region Bau Ig lambda chain V-II region MGC Ig kappa chain V-I region HK101 Antigen CD22:Antigen:p-BCRPSMD6 Ig kappa chain V region EV15 Ig lambda chain V-II region TOG REL PSMB11 MyrG2-PalmC3-LYN IgH heavy chain V-III region VH26 precursor NCK1 IGHV(1-?) STIM1 Ig heavy chain V-I region HG3 ITPR:I(1,4,5)P3tetramerIg heavy chain V-III region BUT NF-kappa-Bp50,p65,c-Rel:IKBI(1,4,5)P3 RELA S-Farn-Me PalmS NRAS I(1,4,5)P3 IGKC p-S559,S644,S652-CARD11 PLCG2 PIK3R1 PSMB5 IGLC2 Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:BTK:NCK1:VAV1:PLCG2BTK IgH heavy chain V-III region VH26 precursor IGHM PTPN6PSMA1 IGKV4-1(21-?) Ig lambda chain V-III region LOI CHUK IGKVA18(21-?) IP3 receptorhomotetramerGRB2-1 Ig kappa chain V-I region HK101 Ig heavy chain V-II region ARH-77 CD19:VAV1Ig kappa chain V-I region HK101 ITPR1 Ig heavy chain V-II region WAH PS IGKV2D-30 SH3KBP1 Ig lambda chain V-II region BOH IKBKG IGLC6 Ig kappa chain V-I region Gal Ig lambda chain V-I region NEW Ig lambda chain V-I region NEWM Ca2+ Ig lambda chain V-II region TOG NF-kappaB:p-IkB:SCF-betaTrCPIg lambda chain V-III region SH Ig kappa chain V-III region VG Ig kappa chain V-I region Gal IGHV(1-?) p-Y188,Y199-CD79A IGHM Ig heavy chain V-II region ARH-77 Ig heavy chain V-II region ARH-77 Ig lambda chain V-III region LOI Ig lambda chain V-III region LOI Ca2+Ig kappa chain V-III region B6 Ig lambda chain V-II region NEI p-Y188,Y199-CD79A Ig kappa chain V-I region BAN IGKV1-5(23-?) Ig heavy chain V-III region WEA NF-kappaBp50,p65,c-Rel dimerIGHM IGLC6 p-Y139-DAPP1 Ig lambda chain V-IV region Kern p-T184-RASGRP1 p-Y188,Y199-CD79A Ig lambda chain V-II region NEI PIP3 activates AKTsignalingp-5Y-BLNK Ig heavy chain V-I region HG3 Ig lambda chain V-II region MGC p-Y196,Y207-CD79B Ig lambda chain V-IV region Kern NFKBIE PSMD8 Ig kappa chain V-I region DEE IGKV4-1(21-?) Ub-21,22-p-S32,S36-NFKBIA PLCG2 Antigen:p-BCR:p-SYKIg kappa chain V-I region BAN IGHV1-2 Ig kappa chain V-II region Cum p-Y188,Y199-CD79A Ig kappa chain V-I region Daudi p-BCL10 IGKV1-12 Ig kappa chain V-III region POM IGLC1 Ig lambda chain V-I region VOR IGKV1-5(23-?) IGHV(1-?) Ig heavy chain V-III region JON IGKV2-28 Ig kappa chain V-I region Daudi ATPIg kappa chain V-I region BAN Ig kappa chain V region EV15 p-CARMA1:MALT1:p-BCL10:TAK1Ig kappa chain V region EV15 UBB(1-76) Ig lambda chain V region 4A IGKC Ig lambda chain V-IV region Kern Ig kappa chain V-II region RPMI 6410 Ig kappa chain V-I region Wes Ig kappa chain V-II region RPMI 6410 IGKVA18(21-?) Ig heavy chain V-II region MCE DAG IGKV1-12 p-CARMA1 OligomerIg lambda chain V-I region VOR Ig kappa chain V-III region B6 Ig kappa chain V-I region HK101 IGLC6 ORAI2 p-6Y-SYK IGKV1-5(23-?) IGKV1-5(23-?) IGKC Ig kappa chain V-II region FR REL UBC(77-152) p-Y196,Y207-CD79B UBC(1-76) Ig lambda chain V-VI region AR IGLC6 Ig kappa chain V-I region AU Ig kappa chain V-I region HK101 Ig kappa chain V-III region B6 Ig heavy chain V-II region OU p-RASGRP1,3:DAGIGKV2D-30 IGHV(1-?) PI(4,5)P2Ig lambda chain V-III region LOI Ig heavy chain V-II region OU IgH heavy chain V-III region VH26 precursor Ig lambda chain V-I region NEWM Ig heavy chain V-III region DOB p-6Y-SYK Ig heavy chain V-III region KOL Ig lambda chain V-II region BOH SOS1 Ig lambda chain V-IV region Bau IGLC3 Ig kappa chain V-I region Wes Ig lambda chain V-II region NEI Tacrolimus Ig lambda chain V-I region NEWM Ig heavy chain V-II region WAH Ig kappa chain V-III region POM GRB2-1 Ig heavy chain V-II region ARH-77 LYN,FYN,BLKIg kappa chain V-II region RPMI 6410 Ig lambda chain V-VI region AR IGLC7 Ig lambda chain V-I region NEWM Ig heavy chain V-II region WAH Ig heavy chain V-III region CAM Ig heavy chain V-III region BRO Ig kappa chain V-III region VG Fe3+ IGKV4-1(21-?) NF-kappaBp50,p65,c-Rel dimerIg kappa chain V-I region Daudi Ig kappa chain V-III region POM Ig heavy chain V-III region KOL Ig kappa chain V-II region RPMI 6410 IGKV4-1(21-?) IKBKG Ig heavy chain V-III region TRO IGHD NF-kappa-Bp50,p65,c-Rel:p-IKBPI(3,4,5)P3 Ig heavy chain V-III region BRO PRKCB Ig lambda chain V-IV region Kern Ig lambda chain V-IV region Hil Ig heavy chain V-I region HG3 Ig kappa chain V-II region Cum Ig kappa chain V-II region FR Ig lambda chain V-VI region AR Zn2+ ATPIGHM Ig kappa chain V-III region VG Ig kappa chain V-III region B6 IGLC7 IGKV4-1(21-?) MALT1 Ig lambda chain V-III region SH RASGRP1 I(1,4,5)P3Ig lambda chain V-II region BOH Ig heavy chain V-II region ARH-77 Ig lambda chain V-I region HA Ig heavy chain V-III region BUT p-Y139-DAPP1:PLCG2:PIP3Ig heavy chain V-II region WAH IGLV(23-?) Ig heavy chain V-I region EU CyclophilinA:Cyclosporin AIg lambda chain V-I region NEW Ig lambda chain V region 4A PSMC1 IGKV4-1(21-?) Ig heavy chain V-II region OU SH3KBP1 CD79B IGLC7 PSMD3 Ig heavy chain V-III region BUT IGKV2D-30 Ig kappa chain V-I region HK101 IGLC6 Ig kappa chain V-I region BAN Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-II region MGC p-BCL10 Ig heavy chain V-III region KOL p-Y762,807,822-CD22:Antigen:p-BCRCalcineurin:Phosphorylated NFATC1,2,3Antigen IGKV3D-20 26S proteasomeIg kappa chain V-I region Wes Ig kappa chain V-II region RPMI 6410 Ig lambda chain V-I region NEWM Ig heavy chain V-I region HG3 Ig kappa chain V-III region VG Ig kappa chain V-I region BAN Ig heavy chain V-III region BRO SOS1 IGHV(1-?) PI(4,5)P2CHUK:IKBKB:IKBKGIg kappa chain V-II region FR Ig heavy chain V-III region BUT Ig lambda chain V-II region BOH IGKV1-12 Ig kappa chain V-I region BAN CUL1 Ig lambda chain V-I region NEW Ig lambda chain V-I region HA Ig lambda chain V-II region NEI TRPC1ATPIGKV2-28 IGLC1 Ig heavy chain V-I region EU DAGPI(3,4,5)P3 Ig heavy chain V-I region EU Ig heavy chain V-III region DOB Ig heavy chain V-III region CAM GRB2-1 SH3KBP1 IGLC6 IGLV(23-?) IGHV(1-?) Ig heavy chain V-I region EU Ig kappa chain V-II region RPMI 6410 IGLC7 IGHV7-81(1-?) p-14S-NFATC2 PhosphorylatedNFATC1,2,3IGHD Ig lambda chain V region 4A Ig heavy chain V-III region DOB Ig kappa chain V-I region Wes SH3KBP1 IGHD MAP3K7Ig heavy chain V-III region CAM Ig lambda chain V region 4A ATPPPP3R1 Ig heavy chain V-I region EU Ig heavy chain V-III region JON Ig heavy chain V-III region DOB Ig kappa chain V-I region AG Ig lambda chain V-III region LOI IGLC2 IGLC3 IGHV7-81(1-?) Ig heavy chain V-II region WAH Ig lambda chain V-I region HA IGKV3D-20 IGLC7 Fe3+ Ig lambda chain V-II region NEI Ig lambda chain V-III region LOI ADPIg lambda chain V-VI region AR Ig lambda chain V-III region SH Ig lambda chain V-III region SH Ig kappa chain V-I region Wes IGKV2-28 IGHV1-2 Ig kappa chain V-III region B6 PSMD14 p-Y188,Y199-CD79A p-Y196,Y207-CD79B Ig lambda chain V-II region MGC p-6Y-SYK CARMA1 oligomerIg kappa chain V-II region FR IGKV2D-30 IGLC2 SOS1 IGLC2 Ig lambda chain V-I region NEWM Ig lambda chain V-II region NEI CARD11 Ig kappa chain V-I region AU BLNK (SLP-65)SignalosomeCa2+ IGKV4-1(21-?) IGHV1-2 PSMC3 STIM1 Ig kappa chain V-I region DEE Ig lambda chain V-III region LOI Ig heavy chain V-III region JON Ig lambda chain V-II region TOG Ig kappa chain V-II region Cum Ig kappa chain V-I region HK101 p-5Y-BLNK IGHV1-2 IGKV1-12 PSMB3 Ig heavy chain V-I region EU NFKBIA Ig lambda chain V-II region MGC BTRC ITPR3 Ig heavy chain V-II region WAH SH3KBP1 Antigen:p-BCR:SYKp21 RAS:GDPGDP p-6Y-SYK IGKVA18(21-?) CALM1:4xCa2+PSMA7 IGLC2 Zn2+ Ig heavy chain V-II region WAH Ig kappa chain V-I region HK101 Ig lambda chain V-I region NEWM ATPIGLC1 Ig heavy chain V-II region WAH Ig lambda chain V-III region SH Ig lambda chain V-IV region Hil Ig heavy chain V-II region ARH-77 IGHV7-81(1-?) IGHV1-2 Ig heavy chain V-III region BRO Ig lambda chain V-I region NEWM IgH heavy chain V-III region VH26 precursor IGHV7-81(1-?) Ig lambda chain V-I region NEWM STIM1 VAV1 Ig heavy chain V-II region OU p-6Y-SYK PRKCBIg heavy chain V-III region DOB Antigen p-Y196,Y207-CD79B p-6Y-SYK BCRUBC(229-304) Ig lambda chain V-I region HA IGHV7-81(1-?) Ig kappa chain V-I region AU Ig heavy chain V-III region BRO Ig kappa chain V-I region AG IGKV2-28 IGKVA18(21-?) MALT1Ig lambda chain V-II region MGC Ig lambda chain V-IV region Kern Ig heavy chain V-III region WEA Ig lambda chain V-I region HA NFKB1(1-433) PSMB6 ADPPSMB1 UBA52(1-76) IGKV2D-30 Ig lambda chain V-II region MGC Ig heavy chain V-III region JON Ig lambda chain V-II region BOH IGHV7-81(1-?) PSMA2 Ig lambda chain V-IV region Kern PSMD12 Ig lambda chain V-VI region AR Ig heavy chain V-I region HG3 RASGRP3 Ig kappa chain V-III region POM RPS27A(1-76) CUL1 IGKV3D-20 Ig lambda chain V region 4A VAV1 Ig kappa chain V-I region Wes IGKV4-1(21-?) Ig lambda chain V-III region SH CHUK VAV1 S-Farn-Me-2xPalmS HRAS FBXW11 Ig lambda chain V-II region TOG PSME3 Ig lambda chain V-I region NEW NAc-CD22NFKBIB IGLC1 Ig kappa chain V-II region Cum IGLC2 Ig lambda chain V-I region NEW IGLC1 Ig kappa chain V-I region AU Ig lambda chain V-I region NEWM Ig lambda chain V-II region TOG IGKC Ig heavy chain V-II region NEWM PSMB7 Ig kappa chain V-III region POM Ig lambda chain V-I region VOR IGKV2-28 MyrG2-PalmC3-LYN Ig lambda chain V-I region NEW Ig kappa chain V-I region AG PPP3CB PPP3CA Ig kappa chain V-I region HK101 REL Ig lambda chain V-IV region Kern Ig lambda chain V-VI region AR Ig lambda chain V-III region LOI Ig kappa chain V-I region Gal Ig kappa chain V-II region FR Ig heavy chain V-III region WEA Ig lambda chain V-I region HA Ig lambda chain V-IV region Bau Ig kappa chain V-I region AG Ig heavy chain V-II region NEWM Ig heavy chain V-I region HG3 MALT1 IGLC3 PLCG2ADPADPCALM1 UBC(533-608) Ig kappa chain V-I region Wes IGLC7 Ig heavy chain V-II region WAH Ig kappa chain V-III region B6 UBB(153-228) IGLC7 p-5Y-BLNK IGHV1-2 Ig heavy chain V-III region TRO Ig kappa chain V-I region Daudi S-Farn-Me KRAS4B Ig heavy chain V-III region BRO ADPCALM1 PI(3,4,5)P3 Ig heavy chain V-III region WEA Ig heavy chain V-II region WAH Ig kappa chain V-I region BAN IGHV1-2 Ig kappa chain V-I region AG p-6Y-SYK PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRIg kappa chain V-I region Daudi CD79A Ig heavy chain V-III region DOB CD79A Ig kappa chain V-II region Cum IGKV1-12 REL PSMD13 IGLC6 IGLC2 IGKV4-1(21-?) Ig heavy chain V-III region TRO IGKV3D-20 Ig kappa chain V-I region BAN Ig heavy chain V-III region DOB Ig lambda chain V-III region LOI Ig heavy chain V-II region ARH-77 Ig heavy chain V-III region DOB Ig heavy chain V-I region EU PTPN6 Ig lambda chain V-IV region Bau Ig lambda chain V-IV region Bau Ig heavy chain V-II region WAH PSMA8 GRB2-1 MAP3K7 Ig kappa chain V-III region B6 Ig heavy chain V-II region MCE Active IKK complexIg lambda chain V-III region SH IGHD Ig kappa chain V-II region Cum p-Y188,Y199-CD79A SYK Ig kappa chain V-I region DEE SOS1 MALT1 Ig kappa chain V-II region RPMI 6410 Ig heavy chain V-III region CAM Antigen:p-BCRVAV1 Ig heavy chain V-III region KOL IGHV1-2 IGLC7 Ig heavy chain V-III region TRO Ig heavy chain V-II region OU IGHM IgH heavy chain V-III region VH26 precursor Ig kappa chain V-I region Daudi STIM1:TRPC1SOS1 BCAP SignalosomeIg lambda chain V-II region NEI p-CD19:VAV1IGHV7-81(1-?) Ig lambda chain V-II region NEI p-Y196,Y207-CD79B Ig heavy chain V-I region HG3 Ig heavy chain V-III region KOL IGLC6 STIM1 DimerIg kappa chain V-I region Gal Ig lambda chain V-I region VOR Ig kappa chain V-I region DEE ADPIGKC Ig heavy chain V-III region WEA p-12S-NFATC1 Ig heavy chain V-I region HG3 Ig heavy chain V-II region ARH-77 Ig heavy chain V-II region MCE IGKV2-28 Ig heavy chain V-III region WEA p-Y223,Y551-BTK STIM1:CalciumIg heavy chain V-I region EU p-14S-NFATC2 Ig lambda chain V-IV region Bau IGKV3D-20 S-Farn-Me-2xPalmS HRAS Ig lambda chain V-I region VOR Ig heavy chain V-II region MCE IGKV2-28 Ig heavy chain V-III region KOL Ig lambda chain V-II region BOH p-12S-NFATC1 Ig lambda chain V-I region HA IGKV1-12 IGLV(23-?) Ig heavy chain V-III region BUT Ig lambda chain V-IV region Bau Ig lambda chain V-IV region Bau p-13S-NFATC3 CD22 IGKVA18(21-?) Ig kappa chain V-II region Cum ITPR2 SKP1 Ig heavy chain V-III region BRO FBXW11 VAV1 Ig lambda chain V-IV region Kern Ig lambda chain V-II region BOH IGHD Ig heavy chain V-II region ARH-77 Ig heavy chain V-II region WAH Ig heavy chain V-II region NEWM Ig heavy chain V-I region EU IGKC p-Y551-BTK IGHV(1-?) IGHV1-2 Antigen IGKV3D-20 SOS1 Ig kappa chain V-I region DEE Ig lambda chain V-II region TOG IGKV2-28 Ig heavy chain V-III region CAM Ig lambda chain V-I region VOR NAc-CD22homo-oligomerNCK1 Ig lambda chain V-II region TOG Ig lambda chain V-II region BOH IGHD Ig kappa chain V-III region POM IGHM Ig kappa chain V-III region B6 p-S243-NFATC2 PSMB2 PIK3CD Ig lambda chain V-IV region Kern Ig kappa chain V-I region Wes Ig lambda chain V-IV region Kern Ig kappa chain V-I region AG Ig lambda chain V-I region VOR PSMC2 IGHM Ig heavy chain V-III region KOL p-Y196,Y207-CD79B IGKV3D-20 Ig heavy chain V-II region NEWM Ig lambda chain V-I region VOR Ig heavy chain V-III region WEA IGLC3 IGHV(1-?) p-S559,S644,S652-CARD11 p-S157,S161-NFKBIE UbIg kappa chain V-I region AG NAD+ Ig kappa chain V region EV15 IGLV(23-?) Ig heavy chain V-III region BRO UBC(457-532) IgH heavy chain V-III region VH26 precursor Ig lambda chain V-I region VOR Ig heavy chain V-III region BUT Ig lambda chain V-IV region Hil VAV1 Ig heavy chain V-III region CAM IGHV7-81(1-?) Ig lambda chain V-IV region Hil Ig kappa chain V-I region Daudi PIK3CD Ig heavy chain V-I region HG3 Ig lambda chain V-I region NEW Ig kappa chain V-III region POM Ig heavy chain V-III region BUT IGHV7-81(1-?) Ig lambda chain V-II region BOH IGKV1-5(23-?) RELA Ig lambda chain V-III region SH Ig lambda chain V-VI region AR IGHV(1-?) RELA 16572, 10091, 16814572, 10028, 40, 109, 1627610176381451458, 97, 105, 145, 16414576767214511714511, 21, 551027611811, 212076102, 123931781, 107, 1691691, 198, 46, 97, 10516814618, 8430, 88, 96, 111


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). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 983705
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  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
  93. Kim YJ, Sekiya F, Poulin B, Bae YS, Rhee SG.; ''Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2.''; PubMed Europe PMC Scholia
  94. Coughlin JJ, Stang SL, Dower NA, Stone JC.; ''RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling.''; PubMed Europe PMC Scholia
  95. Roifman CM, Wang G.; ''Phospholipase C-gamma 1 and phospholipase C-gamma 2 are substrates of the B cell antigen receptor associated protein tyrosine kinase.''; PubMed Europe PMC Scholia
  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
  98. Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D, Maniatis T.; ''Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway.''; PubMed Europe PMC Scholia
  99. Su YW, Zhang Y, Schweikert J, Koretzky GA, Reth M, Wienands J.; ''Interaction of SLP adaptors with the SH2 domain of Tec family kinases.''; PubMed Europe PMC Scholia
  100. Park H, Wahl MI, Afar DE, Turck CW, Rawlings DJ, Tam C, Scharenberg AM, Kinet JP, Witte ON.; ''Regulation of Btk function by a major autophosphorylation site within the SH3 domain.''; PubMed Europe PMC Scholia
  101. Chen TY, Illing M, Molday LL, Hsu YT, Yau KW, Molday RS.; ''Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.''; PubMed Europe PMC Scholia
  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
  103. Suzuki H, Chiba T, Kobayashi M, Takeuchi M, Suzuki T, Ichiyama A, Ikenoue T, Omata M, Furuichi K, Tanaka K.; ''IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2.''; PubMed Europe PMC Scholia
  104. Meller N, Elitzur Y, Isakov N.; ''Protein kinase C-theta (PKCtheta) distribution analysis in hematopoietic cells: proliferating T cells exhibit high proportions of PKCtheta in the particulate fraction.''; PubMed Europe PMC Scholia
  105. Oellerich T, Bremes V, Neumann K, Bohnenberger H, Dittmann K, Hsiao HH, Engelke M, Schnyder T, Batista FD, Urlaub H, Wienands J.; ''The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85.''; PubMed Europe PMC Scholia
  106. Oellerich T, Grønborg M, Neumann K, Hsiao HH, Urlaub H, Wienands J.; ''SLP-65 phosphorylation dynamics reveals a functional basis for signal integration by receptor-proximal adaptor proteins.''; PubMed Europe PMC Scholia
  107. Brooks SR, Kirkham PM, Freeberg L, Carter RH.; ''Binding of cytoplasmic proteins to the CD19 intracellular domain is high affinity, competitive, and multimeric.''; PubMed Europe PMC Scholia
  108. Roifman CM, Ke S.; ''CD19 is a substrate of the antigen receptor-associated protein tyrosine kinase in human B cells.''; PubMed Europe PMC Scholia
  109. Clark MR, Friedrich RJ, Campbell KS, Cambier JC.; ''Human pre-B and B cell membrane mu-chains are noncovalently associated with a disulfide-linked complex containing a product of the B29 gene.''; PubMed Europe PMC Scholia
  110. Yamanashi Y, Kakiuchi T, Mizuguchi J, Yamamoto T, Toyoshima K.; ''Association of B cell antigen receptor with protein tyrosine kinase Lyn.''; PubMed Europe PMC Scholia
  111. Sundivakkam PC, Freichel M, Singh V, Yuan JP, Vogel SM, Flockerzi V, Malik AB, Tiruppathi C.; ''The Ca(2+) sensor stromal interaction molecule 1 (STIM1) is necessary and sufficient for the store-operated Ca(2+) entry function of transient receptor potential canonical (TRPC) 1 and 4 channels in endothelial cells.''; PubMed Europe PMC Scholia
  112. Zandi E, Chen Y, Karin M.; ''Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate.''; PubMed Europe PMC Scholia
  113. Coggeshall KM, McHugh JC, Altman A.; ''Predominant expression and activation-induced tyrosine phosphorylation of phospholipase C-gamma 2 in B lymphocytes.''; PubMed Europe PMC Scholia
  114. Teixeira C, Stang SL, Zheng Y, Beswick NS, Stone JC.; ''Integration of DAG signaling systems mediated by PKC-dependent phosphorylation of RasGRP3.''; PubMed Europe PMC Scholia
  115. Dowler S, Montalvo L, Cantrell D, Morrice N, Alessi DR.; ''Phosphoinositide 3-kinase-dependent phosphorylation of the dual adaptor for phosphotyrosine and 3-phosphoinositides by the Src family of tyrosine kinase.''; PubMed Europe PMC Scholia
  116. Blasioli J, Paust S, Thomas ML.; ''Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22.''; PubMed Europe PMC Scholia
  117. Lorenzo PS, Kung JW, Bottorff DA, Garfield SH, Stone JC, Blumberg PM.; ''Phorbol esters modulate the Ras exchange factor RasGRP3.''; PubMed Europe PMC Scholia
  118. Huai Q, Kim HY, Liu Y, Zhao Y, Mondragon A, Liu JO, Ke H.; ''Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes.''; PubMed Europe PMC Scholia
  119. Yamashita S, Mochizuki N, Ohba Y, Tobiume M, Okada Y, Sawa H, Nagashima K, Matsuda M.; ''CalDAG-GEFIII activation of Ras, R-ras, and Rap1.''; PubMed Europe PMC Scholia
  120. Leprince C, Draves KE, Geahlen RL, Ledbetter JA, Clark EA.; ''CD22 associates with the human surface IgM-B-cell antigen receptor complex.''; PubMed Europe PMC Scholia
  121. Ferguson KM, Kavran JM, Sankaran VG, Fournier E, Isakoff SJ, Skolnik EY, Lemmon MA.; ''Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains.''; PubMed Europe PMC Scholia
  122. Saouaf SJ, Kut SA, Fargnoli J, Rowley RB, Bolen JB, Mahajan S.; ''Reconstitution of the B cell antigen receptor signaling components in COS cells.''; PubMed Europe PMC Scholia
  123. Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-García ME, Ovechkina YL, Rawlings DJ.; ''Phosphorylation of the CARMA1 linker controls NF-kappaB activation.''; PubMed Europe PMC Scholia
  124. Engels N, Wollscheid B, Wienands J.; ''Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha.''; PubMed Europe PMC Scholia
  125. Zhou H, Wertz I, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM.; ''Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO.''; PubMed Europe PMC Scholia
  126. Kim LJ, Ferguson HA, Seto AG, Goodrich JA.; ''Characterization of DNA binding, transcriptional activation, and regulated nuclear association of recombinant human NFATp.''; PubMed Europe PMC Scholia
  127. Tsang E, Giannetti AM, Shaw D, Dinh M, Tse JK, Gandhi S, Ho H, Wang S, Papp E, Bradshaw JM.; ''Molecular mechanism of the Syk activation switch.''; PubMed Europe PMC Scholia
  128. Rebhun JF, Castro AF, Quilliam LA.; ''Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction.''; PubMed Europe PMC Scholia
  129. Ozdener F, Dangelmaier C, Ashby B, Kunapuli SP, Daniel JL.; ''Activation of phospholipase Cgamma2 by tyrosine phosphorylation.''; PubMed Europe PMC Scholia
  130. Cheng KT, Liu X, Ong HL, Ambudkar IS.; ''Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels.''; PubMed Europe PMC Scholia
  131. Traenckner EB, Wilk S, Baeuerle PA.; ''A proteasome inhibitor prevents activation of NF-kappa B and stabilizes a newly phosphorylated form of I kappa B-alpha that is still bound to NF-kappa B.''; PubMed Europe PMC Scholia
  132. Nore BF, Mattsson PT, Antonsson P, Bäckesjö CM, Westlund A, Lennartsson J, Hansson H, Löw P, Rönnstrand L, Smith CI.; ''Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases.''; PubMed Europe PMC Scholia
  133. Roifman CM, Mills GB, Stewart D, Cheung RK, Grinstein S, Gelfand EW.; ''Response of human B cells to different anti-immunoglobulin isotypes: absence of a correlation between early activation events and cell proliferation.''; PubMed Europe PMC Scholia
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  135. Gold MR, Chan VW, Turck CW, DeFranco AL.; ''Membrane Ig cross-linking regulates phosphatidylinositol 3-kinase in B lymphocytes.''; PubMed Europe PMC Scholia
  136. Muik M, Frischauf I, Derler I, Fahrner M, Bergsmann J, Eder P, Schindl R, Hesch C, Polzinger B, Fritsch R, Kahr H, Madl J, Gruber H, Groschner K, Romanin C.; ''Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation.''; PubMed Europe PMC Scholia
  137. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ.; ''TAK1 is a ubiquitin-dependent kinase of MKK and IKK.''; PubMed Europe PMC Scholia
  138. Rolli V, Gallwitz M, Wossning T, Flemming A, Schamel WW, Zürn C, Reth M.; ''Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop.''; PubMed Europe PMC Scholia
  139. Hanasaki K, Powell LD, Varki A.; ''Binding of human plasma sialoglycoproteins by the B cell-specific lectin CD22. Selective recognition of immunoglobulin M and haptoglobin.''; PubMed Europe PMC Scholia
  140. Nisitani S, Kato RM, Rawlings DJ, Witte ON, Wahl MI.; ''In situ detection of activated Bruton's tyrosine kinase in the Ig signaling complex by phosphopeptide-specific monoclonal antibodies.''; PubMed Europe PMC Scholia
  141. Kunkel HG.; ''Surface markers of human lymphocytes.''; PubMed Europe PMC Scholia
  142. Bohnenberger H, Oellerich T, Engelke M, Hsiao HH, Urlaub H, Wienands J.; ''Complex phosphorylation dynamics control the composition of the Syk interactome in B cells.''; PubMed Europe PMC Scholia
  143. Li Z, Nabel GJ.; ''A new member of the I kappaB protein family, I kappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription.''; PubMed Europe PMC Scholia
  144. Rodriguez R, Matsuda M, Perisic O, Bravo J, Paul A, Jones NP, Light Y, Swann K, Williams RL, Katan M.; ''Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling.''; PubMed Europe PMC Scholia
  145. Chiu CW, Dalton M, Ishiai M, Kurosaki T, Chan AC.; ''BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins.''; PubMed Europe PMC Scholia
  146. Alland L, Peseckis SM, Atherton RE, Berthiaume L, Resh MD.; ''Dual myristylation and palmitylation of Src family member p59fyn affects subcellular localization.''; PubMed Europe PMC Scholia
  147. Smith KG, Tarlinton DM, Doody GM, Hibbs ML, Fearon DT.; ''Inhibition of the B cell by CD22: a requirement for Lyn.''; PubMed Europe PMC Scholia
  148. Sanchez M, Misulovin Z, Burkhardt AL, Mahajan S, Costa T, Franke R, Bolen JB, Nussenzweig M.; ''Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta.''; PubMed Europe PMC Scholia
  149. Wu C, Ghosh S.; ''beta-TrCP mediates the signal-induced ubiquitination of IkappaBbeta.''; PubMed Europe PMC Scholia
  150. Okamura H, Aramburu J, García-Rodríguez C, Viola JP, Raghavan A, Tahiliani M, Zhang X, Qin J, Hogan PG, Rao A.; ''Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity.''; PubMed Europe PMC Scholia
  151. Lin L, Czerwinski R, Kelleher K, Siegel MM, Wu P, Kriz R, Aulabaugh A, Stahl M.; ''Activation loop phosphorylation modulates Bruton's tyrosine kinase (Btk) kinase domain activity.''; PubMed Europe PMC Scholia
  152. Nel AE, Landreth GE, Goldschmidt-Clermont PJ, Tung HE, Galbraith RM.; ''Enhanced tyrosine phosphorylation in B lymphocytes upon complexing of membrane immunoglobulin.''; PubMed Europe PMC Scholia
  153. Padeh S, Levitzki A, Gazit A, Mills GB, Roifman CM.; ''Activation of phospholipase C in human B cells is dependent on tyrosine phosphorylation.''; PubMed Europe PMC Scholia
  154. Roose JP, Mollenauer M, Ho M, Kurosaki T, Weiss A.; ''Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes.''; PubMed Europe PMC Scholia
  155. Han S, Collins BE, Bengtson P, Paulson JC.; ''Homomultimeric complexes of CD22 in B cells revealed by protein-glycan cross-linking.''; PubMed Europe PMC Scholia
  156. Salim K, Bottomley MJ, Querfurth E, Zvelebil MJ, Gout I, Scaife R, Margolis RL, Gigg R, Smith CI, Driscoll PC, Waterfield MD, Panayotou G.; ''Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton's tyrosine kinase.''; PubMed Europe PMC Scholia
  157. Wienands J, Schweikert J, Wollscheid B, Jumaa H, Nielsen PJ, Reth M.; ''SLP-65: a new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation.''; PubMed Europe PMC Scholia
  158. Brezski RJ, Monroe JG.; ''B-cell receptor.''; PubMed Europe PMC Scholia
  159. Luik RM, Wang B, Prakriya M, Wu MM, Lewis RS.; ''Oligomerization of STIM1 couples ER calcium depletion to CRAC channel activation.''; PubMed Europe PMC Scholia
  160. Leitges M, Schmedt C, Guinamard R, Davoust J, Schaal S, Stabel S, Tarakhovsky A.; ''Immunodeficiency in protein kinase cbeta-deficient mice.''; PubMed Europe PMC Scholia
  161. Burke JR, Wood MK, Ryseck RP, Walther S, Meyers CA.; ''Peptides corresponding to the N and C termini of IkappaB-alpha, -beta, and -epsilon as probes of the two catalytic subunits of IkappaB kinase, IKK-1 and IKK-2.''; PubMed Europe PMC Scholia
  162. Vasile S, Coligan JE, Yoshida M, Seon BK.; ''Isolation and chemical characterization of the human B29 and mb-1 proteins of the B cell antigen receptor complex.''; PubMed Europe PMC Scholia
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  164. Fu C, Chan AC.; ''Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation.''; PubMed Europe PMC Scholia
  165. Roose JP, Mollenauer M, Gupta VA, Stone J, Weiss A.; ''A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells.''; PubMed Europe PMC Scholia
  166. Blank V, Kourilsky P, Israël A.; ''Cytoplasmic retention, DNA binding and processing of the NF-kappa B p50 precursor are controlled by a small region in its C-terminus.''; PubMed Europe PMC Scholia
  167. McConnell FM, Shears SB, Lane PJ, Scheibel MS, Clark EA.; ''Relationships between the degree of cross-linking of surface immunoglobulin and the associated inositol 1,4,5-trisphosphate and Ca2+ signals in human B 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

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NameTypeDatabase referenceComment
(BTRC:CUL1:SKP1),(FBXW11:CUL1:SKP1)ComplexR-HSA-1168601 (Reactome)
26S proteasomeComplexR-HSA-68819 (Reactome)
ADPMetaboliteCHEBI:456216 (ChEBI)
AHCYL1 ProteinO43865 (Uniprot-TrEMBL)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerComplexR-HSA-5226920 (Reactome)
ATPMetaboliteCHEBI:30616 (ChEBI)
Activated PKC betaComplexR-HSA-139829 (Reactome)
Active IKK complexComplexR-HSA-727820 (Reactome) Co-immunoprecipitation studies and size exclusion chromatography analysis indicate that the high molecular weight (around 700 to 900 kDa) IKK complex is composed of two kinase subunits (IKK1/CHUK/IKBKA and/or IKK2/IKBKB/IKKB) bound to a regulatory gamma subunit (IKBKG/NEMO) (Rothwarf DMet al. 1998; Krappmann D et al. 2000; Miller BS & Zandi E 2001). Variants of the IKK complex containing IKBKA or IKBKB homodimers associated with NEMO may also exist. Crystallographic and quantitative analyses of the binding interactions between N-terminal NEMO and C-terminal IKBKB fragments showed that IKBKB dimers would interact with NEMO dimers resulting in 2:2 stoichiometry (Rushe M et al. 2008). Chemical cross-linking and equilibrium sedimentation analyses of IKBKG (NEMO) suggest a tetrameric oligomerization (dimers of dimers) (Tegethoff S et al. 2003). The tetrameric NEMO could sequester four kinase molecules, yielding an 2xIKBKA:2xIKBKB:4xNEMO stoichiometry (Tegethoff S et al. 2003). The above data suggest that the core IKK complex consists of an IKBKA:IKBKB heterodimer associated with an IKBKG dimer or higher oligomeric assemblies. However, the exact stoichiometry of the IKK complex remains unclear.
Antigen R-ALL-173548 (Reactome)
Antigen R-ALL-983667 (Reactome)
Antigen:BCRComplexR-HSA-983689 (Reactome)
Antigen:p-BCR:SYKComplexR-HSA-983693 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:BTK:NCK1:VAV1:PLCG2ComplexR-HSA-9606167 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y223,Y551-BTK:NCK1:VAV1:PLCG2ComplexR-HSA-9606153 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y551-BTK:NCK1:VAV1:PLCG2ComplexR-HSA-9606149 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1ComplexR-HSA-983687 (Reactome)
Antigen:p-BCR:p-SYKComplexR-HSA-983690 (Reactome)
Antigen:p-BCRComplexR-HSA-983691 (Reactome)
AntigenR-ALL-983667 (Reactome)
BCAP SignalosomeComplexR-HSA-2045909 (Reactome)
BCRComplexR-HSA-983677 (Reactome)
BLNK (SLP-65) SignalosomeComplexR-HSA-984818 (Reactome)
BLNK ProteinQ8WV28 (Uniprot-TrEMBL)
BLNK:GRB2:SOS1:CIN85ComplexR-HSA-983692 (Reactome)
BTK ProteinQ06187 (Uniprot-TrEMBL)
BTKProteinQ06187 (Uniprot-TrEMBL)
BTRC ProteinQ9Y297 (Uniprot-TrEMBL)
CALM1 ProteinP0DP23 (Uniprot-TrEMBL)
CALM1:4xCa2+ComplexR-HSA-74294 (Reactome)
CALM1ProteinP0DP23 (Uniprot-TrEMBL)
CARD11 ProteinQ9BXL7 (Uniprot-TrEMBL)
CARMA1 oligomerComplexR-HSA-1169088 (Reactome)
CD19 ProteinP15391 (Uniprot-TrEMBL)
CD19 SignalosomeComplexR-HSA-2076233 (Reactome)
CD19:VAV1ComplexR-HSA-2076225 (Reactome)
CD22 ProteinP20273 (Uniprot-TrEMBL)
CD22:Antigen:p-BCRComplexR-HSA-5690660 (Reactome)
CD22ProteinP20273 (Uniprot-TrEMBL)
CD79A ProteinP11912 (Uniprot-TrEMBL)
CD79B ProteinP40259 (Uniprot-TrEMBL)
CHUK ProteinO15111 (Uniprot-TrEMBL)
CHUK:IKBKB:IKBKGComplexR-HSA-168113 (Reactome) Co-immunoprecipitation studies and size exclusion chromatography analysis indicate that the high molecular weight (around 700 to 900 kDa) IKK complex is composed of two kinase subunits (IKK1/CHUK/IKBKA and/or IKK2/IKBKB/IKKB) bound to a regulatory gamma subunit (IKBKG/NEMO) (Rothwarf DMet al. 1998; Krappmann D et al. 2000; Miller BS & Zandi E 2001). Variants of the IKK complex containing IKBKA or IKBKB homodimers associated with NEMO may also exist. Crystallographic and quantitative analyses of the binding interactions between N-terminal NEMO and C-terminal IKBKB fragments showed that IKBKB dimers would interact with NEMO dimers resulting in 2:2 stoichiometry (Rushe M et al. 2008). Chemical cross-linking and equilibrium sedimentation analyses of IKBKG (NEMO) suggest a tetrameric oligomerization (dimers of dimers) (Tegethoff S et al. 2003). The tetrameric NEMO could sequester four kinase molecules, yielding an 2xIKBKA:2xIKBKB:4xNEMO stoichiometry (Tegethoff S et al. 2003). The above data suggest that the core IKK complex consists of an IKBKA:IKBKB heterodimer associated with an IKBKG dimer or higher oligomeric assemblies. However, the exact stoichiometry of the IKK complex remains unclear.
CRAC channelComplexR-HSA-434679 (Reactome)
CUL1 ProteinQ13616 (Uniprot-TrEMBL)
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
Calcineurin (CaN)ComplexR-HSA-2025977 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3ComplexR-HSA-2025899 (Reactome)
Cyclophilin A:Cyclosporin AComplexR-HSA-2026008 (Reactome)
Cyclosporin A MetaboliteCHEBI:4031 (ChEBI)
DAG MetaboliteCHEBI:17815 (ChEBI)
DAGMetaboliteCHEBI:17815 (ChEBI)
DAPP1ProteinQ9UN19 (Uniprot-TrEMBL)
Dephosphorylated NFATC1,2,3ComplexR-HSA-2025852 (Reactome)
FBXW11 ProteinQ9UKB1 (Uniprot-TrEMBL)
FKBP1A ProteinP62942 (Uniprot-TrEMBL)
FKBP1A:TacrolimusComplexR-HSA-2026019 (Reactome)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GRB2-1 ProteinP62993-1 (Uniprot-TrEMBL)
GRB2-1ProteinP62993-1 (Uniprot-TrEMBL)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
I(1,4,5)P3 MetaboliteCHEBI:16595 (ChEBI)
I(1,4,5)P3MetaboliteCHEBI:16595 (ChEBI)
IGHD ProteinP01880 (Uniprot-TrEMBL)
IGHM ProteinP01871 (Uniprot-TrEMBL)
IGHV(1-?) ProteinA2KUC3 (Uniprot-TrEMBL)
IGHV1-2 ProteinP23083 (Uniprot-TrEMBL)
IGHV7-81(1-?) ProteinQ6PIL0 (Uniprot-TrEMBL)
IGKC ProteinP01834 (Uniprot-TrEMBL)
IGKV1-12 ProteinA0A0C4DH73 (Uniprot-TrEMBL)
IGKV1-5(23-?) ProteinP01602 (Uniprot-TrEMBL)
IGKV2-28 ProteinA0A075B6P5 (Uniprot-TrEMBL)
IGKV2D-30 ProteinA0A075B6S6 (Uniprot-TrEMBL)
IGKV3D-20 ProteinA0A0C4DH25 (Uniprot-TrEMBL)
IGKV4-1(21-?) ProteinP06312 (Uniprot-TrEMBL)
IGKVA18(21-?) ProteinA2NJV5 (Uniprot-TrEMBL)
IGLC1 ProteinP0CG04 (Uniprot-TrEMBL)
IGLC2 ProteinP0DOY2 (Uniprot-TrEMBL)
IGLC3 ProteinP0DOY3 (Uniprot-TrEMBL)
IGLC6 ProteinP0CF74 (Uniprot-TrEMBL)
IGLC7 ProteinA0M8Q6 (Uniprot-TrEMBL)
IGLV(23-?) ProteinA2NXD2 (Uniprot-TrEMBL)
IKBKB ProteinO14920 (Uniprot-TrEMBL)
IKBKG ProteinQ9Y6K9 (Uniprot-TrEMBL)
IP3 receptor homotetramerComplexR-HSA-169686 (Reactome)
ITPR1 ProteinQ14643 (Uniprot-TrEMBL)
ITPR2 ProteinQ14571 (Uniprot-TrEMBL)
ITPR3 ProteinQ14573 (Uniprot-TrEMBL)
ITPR:I(1,4,5)P3 tetramerComplexR-HSA-169696 (Reactome)
Ig heavy chain V-I region EU ProteinP01742 (Uniprot-TrEMBL)
Ig heavy chain V-I region HG3 ProteinP01743 (Uniprot-TrEMBL)
Ig heavy chain V-II region ARH-77 ProteinP06331 (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 WAH ProteinP01824 (Uniprot-TrEMBL)
Ig heavy chain V-III region BRO ProteinP01766 (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 JON ProteinP01780 (Uniprot-TrEMBL)
Ig heavy chain V-III region KOL ProteinP01772 (Uniprot-TrEMBL)
Ig heavy chain V-III region TRO ProteinP01762 (Uniprot-TrEMBL)
Ig heavy chain V-III region WEA ProteinP01763 (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 DEE ProteinP01597 (Uniprot-TrEMBL)
Ig kappa chain V-I region Daudi ProteinP04432 (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 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 RPMI 6410 ProteinP06310 (Uniprot-TrEMBL)
Ig kappa chain V-III region B6 ProteinP01619 (Uniprot-TrEMBL)
Ig kappa chain V-III region POM ProteinP01624 (Uniprot-TrEMBL)
Ig kappa chain V-III region VG ProteinP04433 (Uniprot-TrEMBL)
Ig lambda chain V region 4A ProteinP04211 (Uniprot-TrEMBL)
Ig lambda chain V-I region HA ProteinP01700 (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 VOR ProteinP01699 (Uniprot-TrEMBL)
Ig lambda chain V-II region BOH ProteinP01706 (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 TOG ProteinP01704 (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-VI region AR ProteinP01721 (Uniprot-TrEMBL)
IgH heavy chain V-III region VH26 precursor ProteinP01764 (Uniprot-TrEMBL)
LYN, p-SYKComplexR-HSA-9606888 (Reactome)
LYN,FYN,BLKComplexR-HSA-9606895 (Reactome)
MALT1 ProteinQ9UDY8 (Uniprot-TrEMBL)
MALT1ProteinQ9UDY8 (Uniprot-TrEMBL)
MAP3K7 ProteinO43318 (Uniprot-TrEMBL)
MAP3K7ProteinO43318 (Uniprot-TrEMBL)
MyrG2-BLK ProteinP51451 (Uniprot-TrEMBL)
MyrG2-PalmC3,6-FYN ProteinP06241 (Uniprot-TrEMBL)
MyrG2-PalmC3-LYN ProteinP07948 (Uniprot-TrEMBL)
MyrG2-PalmC3-LYNProteinP07948 (Uniprot-TrEMBL)
NAD+ MetaboliteCHEBI:57540 (ChEBI)
NAc-CD22 homo-oligomerR-HSA-5690698 (Reactome)
NAc-CD22ProteinP20273 (Uniprot-TrEMBL)
NCK1 ProteinP16333 (Uniprot-TrEMBL)
NCK1ProteinP16333 (Uniprot-TrEMBL)
NF-kappa-B p50,p65,c-Rel:IKBComplexR-HSA-1168593 (Reactome)
NF-kappa-B p50,p65,c-Rel:p-IKBComplexR-HSA-1168588 (Reactome)
NF-kappaB p50,p65,c-Rel dimerComplexR-HSA-1168598 (Reactome)
NF-kappaB p50,p65,c-Rel dimerComplexR-HSA-1168608 (Reactome)
NF-kappaB p50,p65,c-Rel:ub-p-IKBComplexR-HSA-1168613 (Reactome)
NF-kappaB:p-IkB:SCF-betaTrCPComplexR-HSA-1168617 (Reactome)
NFKB1(1-433) ProteinP19838 (Uniprot-TrEMBL)
NFKBIA ProteinP25963 (Uniprot-TrEMBL)
NFKBIB ProteinQ15653 (Uniprot-TrEMBL)
NFKBIE ProteinO00221 (Uniprot-TrEMBL)
ORAI dimerComplexR-HSA-8862646 (Reactome)
ORAI1 ProteinQ96D31 (Uniprot-TrEMBL)
ORAI2 ProteinQ96SN7 (Uniprot-TrEMBL)
PI(3,4,5)P3 MetaboliteCHEBI:16618 (ChEBI)
PI(3,4,5)P3MetaboliteCHEBI:16618 (ChEBI)
PI(4,5)P2MetaboliteCHEBI:18348 (ChEBI)
PIK3CD ProteinO00329 (Uniprot-TrEMBL)
PIK3CD:PIK3R1ComplexR-HSA-1806213 (Reactome)
PIK3R1 ProteinP27986 (Uniprot-TrEMBL)
PIP3 activates AKT signalingPathwayR-HSA-1257604 (Reactome) Signaling by AKT is one of the key outcomes of receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimulated cells, PI3K class IA enzymes reside in the cytosol as inactive heterodimers composed of p85 regulatory subunit and p110 catalytic subunit. In this complex, p85 stabilizes p110 while inhibiting its catalytic activity. Upon binding of extracellular ligands to RTKs, receptors dimerize and undergo autophosphorylation. The regulatory subunit of PI3K, p85, is recruited to phosphorylated cytosolic RTK domains either directly or indirectly, through adaptor proteins, leading to a conformational change in the PI3K IA heterodimer that relieves inhibition of the p110 catalytic subunit. Activated PI3K IA phosphorylates PIP2, converting it to PIP3; this reaction is negatively regulated by PTEN phosphatase. PIP3 recruits AKT to the plasma membrane, allowing TORC2 to phosphorylate a conserved serine residue of AKT. Phosphorylation of this serine induces a conformation change in AKT, exposing a conserved threonine residue that is then phosphorylated by PDPK1 (PDK1). Phosphorylation of both the threonine and the serine residue is required to fully activate AKT. The active AKT then dissociates from PIP3 and phosphorylates a number of cytosolic and nuclear proteins that play important roles in cell survival and metabolism. For a recent review of AKT signaling, please refer to Manning and Cantley, 2007.
PLCG2 ProteinP16885 (Uniprot-TrEMBL)
PLCG2ProteinP16885 (Uniprot-TrEMBL)
PPIA ProteinP62937 (Uniprot-TrEMBL)
PPP3CA ProteinQ08209 (Uniprot-TrEMBL)
PPP3CB ProteinP16298 (Uniprot-TrEMBL)
PPP3R1 ProteinP63098 (Uniprot-TrEMBL)
PRKCB ProteinP05771 (Uniprot-TrEMBL)
PRKCBProteinP05771 (Uniprot-TrEMBL)
PS MetaboliteCHEBI:18303 (ChEBI)
PSMetaboliteCHEBI:18303 (ChEBI)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (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)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (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)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (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)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
PTPN6 ProteinP29350 (Uniprot-TrEMBL)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRComplexR-HSA-5690677 (Reactome)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
Phosphorylated NFATC1,2,3ComplexR-HSA-2025924 (Reactome)
RASGRP1 ProteinO95267 (Uniprot-TrEMBL)
RASGRP1,3ComplexR-HSA-1169462 (Reactome)
RASGRP3 ProteinQ8IV61 (Uniprot-TrEMBL)
REL ProteinQ04864 (Uniprot-TrEMBL)
RELA ProteinQ04206 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
S-Farn-Me KRAS4B ProteinP01116-2 (Uniprot-TrEMBL)
S-Farn-Me PalmS NRAS ProteinP01111 (Uniprot-TrEMBL)
S-Farn-Me-2xPalmS HRAS ProteinP01112 (Uniprot-TrEMBL)
S-Farn-Me-PalmS KRAS4A ProteinP01116-1 (Uniprot-TrEMBL)
SH3KBP1 ProteinQ96B97 (Uniprot-TrEMBL)
SHFM1 ProteinP60896 (Uniprot-TrEMBL)
SKP1 ProteinP63208 (Uniprot-TrEMBL)
SOS1 ProteinQ07889 (Uniprot-TrEMBL)
STIM1 DimerComplexR-HSA-1168370 (Reactome)
STIM1 ProteinQ13586 (Uniprot-TrEMBL)
STIM1:CalciumComplexR-HSA-1168371 (Reactome)
STIM1:TRPC1ComplexR-HSA-2089954 (Reactome)
SYK ProteinP43405 (Uniprot-TrEMBL)
SYKProteinP43405 (Uniprot-TrEMBL)
TRPC1 ProteinP48995 (Uniprot-TrEMBL)
TRPC1ProteinP48995 (Uniprot-TrEMBL)
Tacrolimus MetaboliteCHEBI:61049 (ChEBI)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
Ub-21,22-p-S32,S36-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (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-4Y-PIK3AP1ProteinQ6ZUJ8 (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 OligomerComplexR-HSA-1168616 (Reactome) The coiled coil (CC) domain of CARMA1 interacts with the CC domain on other CARMA1 molecules to form oligomers of unknown stoichiometry.
p-CARMA1:MALT1:p-BCL10:TAK1:IKKComplexR-HSA-1168620 (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.
p-CARMA1:MALT1:p-BCL10:TAK1ComplexR-HSA-1168619 (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.
p-CARMA1:MALT1:p-BCL10ComplexR-HSA-1168622 (Reactome)
p-CD19:VAV1ComplexR-HSA-9606889 (Reactome)
p-RASGRP1,3:DAGComplexR-HSA-1168369 (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-S243-NFATC2 ProteinQ13469 (Uniprot-TrEMBL)
p-S257-NFATC1 ProteinO95644 (Uniprot-TrEMBL)
p-S265-NFATC3 ProteinQ12968 (Uniprot-TrEMBL)
p-S32,S36-NFKBIA ProteinP25963 (Uniprot-TrEMBL)
p-S559,S644,S652-CARD11 ProteinQ9BXL7 (Uniprot-TrEMBL)
p-T133-RASGRP3 ProteinQ8IV61 (Uniprot-TrEMBL)
p-T184-RASGRP1 ProteinO95267 (Uniprot-TrEMBL)
p-Y139-DAPP1 ProteinQ9UN19 (Uniprot-TrEMBL)
p-Y139-DAPP1:PIP3ComplexR-HSA-1168366 (Reactome)
p-Y139-DAPP1:PLCG2:PIP3ComplexR-HSA-9606886 (Reactome)
p-Y188,Y199-CD79A ProteinP11912 (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-Y551-BTK ProteinQ06187 (Uniprot-TrEMBL)
p-Y753,Y759,Y1217-PLCG2 ProteinP16885 (Uniprot-TrEMBL)
p-Y762,807,822-CD22 ProteinP20273 (Uniprot-TrEMBL)
p-Y762,807,822-CD22:Antigen:p-BCRComplexR-HSA-5690689 (Reactome)
p21 RAS:GDPComplexR-HSA-109796 (Reactome)
p21 RAS:GTPComplexR-HSA-109783 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
(BTRC:CUL1:SKP1),(FBXW11:CUL1:SKP1)ArrowR-HSA-1168643 (Reactome)
(BTRC:CUL1:SKP1),(FBXW11:CUL1:SKP1)R-HSA-1168642 (Reactome)
26S proteasomemim-catalysisR-HSA-1168640 (Reactome)
ADPArrowR-HSA-1168374 (Reactome)
ADPArrowR-HSA-1168635 (Reactome)
ADPArrowR-HSA-1168638 (Reactome)
ADPArrowR-HSA-1168641 (Reactome)
ADPArrowR-HSA-5690702 (Reactome)
ADPArrowR-HSA-9606159 (Reactome)
ADPArrowR-HSA-9606162 (Reactome)
ADPArrowR-HSA-9606163 (Reactome)
ADPArrowR-HSA-9606883 (Reactome)
ADPArrowR-HSA-9606884 (Reactome)
ADPArrowR-HSA-983703 (Reactome)
ADPArrowR-HSA-983707 (Reactome)
ADPArrowR-HSA-983709 (Reactome)
AHCYL1:NAD+:ITPR1:I(1,4,5)P3 tetramerTBarR-HSA-169683 (Reactome)
ATPR-HSA-1168374 (Reactome)
ATPR-HSA-1168635 (Reactome)
ATPR-HSA-1168638 (Reactome)
ATPR-HSA-1168641 (Reactome)
ATPR-HSA-5690702 (Reactome)
ATPR-HSA-9606159 (Reactome)
ATPR-HSA-9606162 (Reactome)
ATPR-HSA-9606163 (Reactome)
ATPR-HSA-9606883 (Reactome)
ATPR-HSA-9606884 (Reactome)
ATPR-HSA-983703 (Reactome)
ATPR-HSA-983707 (Reactome)
ATPR-HSA-983709 (Reactome)
Activated PKC betaArrowR-HSA-1168373 (Reactome)
Activated PKC betamim-catalysisR-HSA-1168635 (Reactome)
Active IKK complexArrowR-HSA-1168641 (Reactome)
Active IKK complexmim-catalysisR-HSA-1168638 (Reactome)
Antigen:BCRArrowR-HSA-983696 (Reactome)
Antigen:BCRR-HSA-983709 (Reactome)
Antigen:p-BCR:SYKArrowR-HSA-983700 (Reactome)
Antigen:p-BCR:SYKR-HSA-983707 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:BTK:NCK1:VAV1:PLCG2ArrowR-HSA-9606151 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:BTK:NCK1:VAV1:PLCG2R-HSA-9606163 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y223,Y551-BTK:NCK1:VAV1:PLCG2ArrowR-HSA-9606159 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y223,Y551-BTK:NCK1:VAV1:PLCG2R-HSA-9606162 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y223,Y551-BTK:NCK1:VAV1:PLCG2mim-catalysisR-HSA-9606162 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y551-BTK:NCK1:VAV1:PLCG2ArrowR-HSA-9606163 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y551-BTK:NCK1:VAV1:PLCG2R-HSA-9606159 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1:p-Y551-BTK:NCK1:VAV1:PLCG2mim-catalysisR-HSA-9606159 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1ArrowR-HSA-983703 (Reactome)
Antigen:p-BCR:p-SYK:p-BLNK:CIN85:GRB2:SOS1R-HSA-9606151 (Reactome)
Antigen:p-BCR:p-SYKArrowR-HSA-983707 (Reactome)
Antigen:p-BCR:p-SYKR-HSA-983703 (Reactome)
Antigen:p-BCR:p-SYKmim-catalysisR-HSA-983703 (Reactome)
Antigen:p-BCR:p-SYKmim-catalysisR-HSA-983707 (Reactome)
Antigen:p-BCRArrowR-HSA-983709 (Reactome)
Antigen:p-BCRR-HSA-5690740 (Reactome)
Antigen:p-BCRR-HSA-983700 (Reactome)
AntigenR-HSA-983696 (Reactome)
BCAP SignalosomeArrowR-HSA-9606160 (Reactome)
BCAP Signalosomemim-catalysisR-HSA-2045911 (Reactome)
BCRR-HSA-983696 (Reactome)
BLNK (SLP-65) SignalosomeArrowR-HSA-9606162 (Reactome)
BLNK (SLP-65) Signalosomemim-catalysisR-HSA-1112666 (Reactome)
BLNK:GRB2:SOS1:CIN85R-HSA-983703 (Reactome)
BTKR-HSA-9606151 (Reactome)
CALM1:4xCa2+ArrowR-HSA-74448 (Reactome)
CALM1:4xCa2+R-HSA-2025890 (Reactome)
CALM1R-HSA-74448 (Reactome)
CARMA1 oligomerR-HSA-1168635 (Reactome)
CD19 SignalosomeArrowR-HSA-9606887 (Reactome)
CD19 Signalosomemim-catalysisR-HSA-2076220 (Reactome)
CD19:VAV1R-HSA-9606883 (Reactome)
CD22:Antigen:p-BCRArrowR-HSA-5690740 (Reactome)
CD22:Antigen:p-BCRR-HSA-5690702 (Reactome)
CD22R-HSA-5690740 (Reactome)
CHUK:IKBKB:IKBKGR-HSA-1168637 (Reactome)
CRAC channelArrowR-HSA-434700 (Reactome)
CRAC channelmim-catalysisR-HSA-434798 (Reactome)
Ca2+ArrowR-HSA-1168376 (Reactome)
Ca2+ArrowR-HSA-169683 (Reactome)
Ca2+ArrowR-HSA-2089943 (Reactome)
Ca2+ArrowR-HSA-434798 (Reactome)
Ca2+R-HSA-1168373 (Reactome)
Ca2+R-HSA-169683 (Reactome)
Ca2+R-HSA-2025890 (Reactome)
Ca2+R-HSA-2089943 (Reactome)
Ca2+R-HSA-434798 (Reactome)
Ca2+R-HSA-74448 (Reactome)
Calcineurin (CaN)R-HSA-2025890 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3ArrowR-HSA-2025890 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3R-HSA-2025882 (Reactome)
Calcineurin:Phosphorylated NFATC1,2,3mim-catalysisR-HSA-2025882 (Reactome)
Cyclophilin A:Cyclosporin ATBarR-HSA-2025882 (Reactome)
DAGArrowR-HSA-1112666 (Reactome)
DAGR-HSA-1168373 (Reactome)
DAGR-HSA-1168374 (Reactome)
DAPP1R-HSA-9606884 (Reactome)
Dephosphorylated NFATC1,2,3ArrowR-HSA-2025882 (Reactome)
FKBP1A:TacrolimusTBarR-HSA-2025882 (Reactome)
GDPArrowR-HSA-1168636 (Reactome)
GRB2-1R-HSA-9606887 (Reactome)
GTPR-HSA-1168636 (Reactome)
I(1,4,5)P3ArrowR-HSA-1112666 (Reactome)
I(1,4,5)P3ArrowR-HSA-169683 (Reactome)
I(1,4,5)P3R-HSA-169680 (Reactome)
IP3 receptor homotetramerR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramerArrowR-HSA-169680 (Reactome)
ITPR:I(1,4,5)P3 tetramermim-catalysisR-HSA-1168376 (Reactome)
ITPR:I(1,4,5)P3 tetramermim-catalysisR-HSA-169683 (Reactome)
LYN, p-SYKmim-catalysisR-HSA-9606163 (Reactome)
LYN,FYN,BLKmim-catalysisR-HSA-983709 (Reactome)
MALT1R-HSA-1168644 (Reactome)
MAP3K7R-HSA-1168637 (Reactome)
MyrG2-PalmC3-LYNmim-catalysisR-HSA-5690702 (Reactome)
NAc-CD22 homo-oligomerArrowR-HSA-5690669 (Reactome)
NAc-CD22R-HSA-5690669 (Reactome)
NCK1R-HSA-9606151 (Reactome)
NF-kappa-B p50,p65,c-Rel:IKBR-HSA-1168638 (Reactome)
NF-kappa-B p50,p65,c-Rel:p-IKBArrowR-HSA-1168638 (Reactome)
NF-kappa-B p50,p65,c-Rel:p-IKBR-HSA-1168642 (Reactome)
NF-kappaB p50,p65,c-Rel dimerArrowR-HSA-1168633 (Reactome)
NF-kappaB p50,p65,c-Rel dimerArrowR-HSA-1168640 (Reactome)
NF-kappaB p50,p65,c-Rel dimerR-HSA-1168633 (Reactome)
NF-kappaB p50,p65,c-Rel:ub-p-IKBArrowR-HSA-1168643 (Reactome)
NF-kappaB p50,p65,c-Rel:ub-p-IKBR-HSA-1168640 (Reactome)
NF-kappaB:p-IkB:SCF-betaTrCPArrowR-HSA-1168642 (Reactome)
NF-kappaB:p-IkB:SCF-betaTrCPR-HSA-1168643 (Reactome)
ORAI dimerR-HSA-434700 (Reactome)
PI(3,4,5)P3ArrowR-HSA-2045911 (Reactome)
PI(3,4,5)P3ArrowR-HSA-2076220 (Reactome)
PI(3,4,5)P3R-HSA-9606151 (Reactome)
PI(3,4,5)P3R-HSA-9606884 (Reactome)
PI(4,5)P2R-HSA-1112666 (Reactome)
PI(4,5)P2R-HSA-2045911 (Reactome)
PI(4,5)P2R-HSA-2076220 (Reactome)
PIK3CD:PIK3R1R-HSA-9606160 (Reactome)
PIK3CD:PIK3R1R-HSA-9606887 (Reactome)
PLCG2R-HSA-9606151 (Reactome)
PLCG2R-HSA-9606894 (Reactome)
PRKCBR-HSA-1168373 (Reactome)
PSR-HSA-1168373 (Reactome)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRArrowR-HSA-5690701 (Reactome)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRTBarR-HSA-983707 (Reactome)
PTPN6:p-Y762,807,822-CD22:Antigen:p-BCRTBarR-HSA-983709 (Reactome)
PTPN6R-HSA-5690701 (Reactome)
Phosphorylated NFATC1,2,3R-HSA-2025890 (Reactome)
R-HSA-1112666 (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).
R-HSA-1168373 (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).
R-HSA-1168374 (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).
R-HSA-1168376 (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).
R-HSA-1168633 (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)
R-HSA-1168635 (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.
R-HSA-1168636 (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.
R-HSA-1168637 (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).
R-HSA-1168638 (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).
R-HSA-1168640 (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).
R-HSA-1168641 (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.
R-HSA-1168642 (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).
R-HSA-1168643 (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).
R-HSA-1168644 (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).
R-HSA-169680 (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.
R-HSA-169683 (Reactome) IP3 promotes the release of intracellular calcium.
R-HSA-2025882 (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).
R-HSA-2025890 (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).
R-HSA-2045911 (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).)
R-HSA-2076220 (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).)
R-HSA-2089927 (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).
R-HSA-2089943 (Reactome) TRPC1 forms a channel that transports Ca2+ across the plasma membrane. TRPC1 is gated by STIM1 (Ong et al. 2007).
R-HSA-434700 (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 Orai to form a calcium-release activated calcium (CRAC) channel.
R-HSA-434798 (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.
R-HSA-5690669 (Reactome) In resting B cells, CD22 is a prominent cis ligand for itself, forming CD22 homo-oligomers. Cross-linking experiments showed that CD22 primarily recognizes alpha2,6-linked sialic acid (2,6Sia or N-acetylneuraminic acid (NAc)) on neighboring CD22 molecules present on the same B-cell (Han et al. 2005). NH2-terminal immuno globulin (Ig) domains, Ig1 and Ig2, mediate 2,6Sia binding (Law et al. 1998, Jin et al. 2002). Thus, CD22 recognizes self structures and triggers inhibitory signals, which may be relevant for suppression of autoimmune B-cell responses.
R-HSA-5690701 (Reactome) The phosphorylated ITIMs of CD22 facilitates recruitment of the tyrosine phosphatase SHP1 (Src homology region 2 domain-containing phosphatase-1 also referred as PTPN6/Tyrosine-protein phosphatase non-receptor type 6), which down modulates BCR signalling (Doody et al. 1995). Activation of SHP1 regulates the strength of the BCR-induced Ca+2 signal. Regulation of Ca+2 signalling occurs both by dephosphorylation of intracellular SHP1 substrates which are important for triggering of Ca+2 signals (Adachi et al. 2001, Stebbins et al. 2003), as well as by a SHP1 dependent activation of the Ca+2 plasma membrane pump PMCA4 which controls termination of the signal (Muller et al. 2013, Ghosh et al. 2006).
R-HSA-5690702 (Reactome) After ligation of membrane-bound IgM, CD22 is quickly tyrosine phosphorylated on its cytoplasmic ITIM sequence (immunoreceptor tyrosine-based inhibition motif). The tyrosine kinase involved in CD22 phosphorylation is LYN, a member of the Src kinase family (Smith et al. 1998). The CD22 cytoplasmic tail contains six tyrosines, three of which belong to the ITIM sequence (Nitschke & Tsubata 2004).
R-HSA-5690740 (Reactome) Physical association of CD22 with the BCR seems to have direct involvement in the regulation of BCR signalling, as antibody-mediated clustering of CD22 with the BCR leads to dampened signaling (Smith et al. 1998), and evidence of their association has been obtained by confocal microscopy, coimmunoprecipitation and chemical crossing (Zhang et al. 2004, Phee et al. 2001, Peaker et al. 1993, Law et al. 1994, Leprince et al. 1993, Collins et al. 2006). Forced ligation of CD22 to the BCR dramatically increases CD22 phosphorylation and suppression of BCR signalling (Macauley, 2013). This is relevant to suppression of BCR signalling to membrane antigens on B cells that contain self sialic acids (Lanoue, 2002; Macauley 2013). CD22 ligand binding modulates its activity as a negative regulator of B cell signalling.
R-HSA-74448 (Reactome) Upon increase in calcium concentration, calmodulin (CaM) is activated by binding to four calcium ions (Crouch and Klee 1980).
R-HSA-9606151 (Reactome) Phosphorylated BLNK (also called BASH or SLP-65) at the plasma membrane recruits BTK, PLC gamma, VAV, GRB2, and NCK (Fu and Chan 1997, Fu et al. 1998, Wienands et al. 1998, Su et al. 1999, Baba et al. 2001, Chiu et al. 2002). The SH2 domain of BTK binds phosphorylated BLNK (Hashimoto et al. 1999, Su et al. 1999, Baba et al. 2001). BLNK is constitutively bound to CIN85 and phosphorylated BLNK is bound to a large complex containing CIN85, SOS1, GRB2, phosphorylated SYK, and the B cell receptor.
R-HSA-9606159 (Reactome) After phosphorylation on tyrosine-551 by LYN or SYK, BTK autophosphorylates tyrosine-223 (Wahl et al. 1997, Nore et al. 2003, and inferred from mouse homologs). Maximum autophosphorylation occurs 5 minutes after activation of the B cell receptor and returns to low phosphorylation after 30 minutes (Nisitani et al. 1999).
R-HSA-9606160 (Reactome) Phosphorylated PIK3AP1 (BCAP) binds the p85 subunit of phosphoinositide 3-kinase (PI3K) (inferred from chicken homologs). PIK3AP1 is phosphorylated by LYN in response to activation of CD19.
R-HSA-9606162 (Reactome) Activated BTK (BTK phosphorylated on tyrosine-551 and tyrosine-223) bound to phosphorylated BLNK phosphorylates phospholipase gamma-2 (PKCG2) on tyrosines 753, 759, and 1217 (Rodriguez et al. 2001 and inferred from the rat homolog) thereby activating PLCG2 to hydrolyze phosphatidylinositol 4,5-bisphosphate, yielding the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (Carter et al. 1991, Roifman and Wang 1992, Kim et al. 2004, Sekiya et al. 2004). PLCG2 also binds phosphoinositol 3,4,5-trisphosphate (PIP3) produced by PI3K at the plasma membrane.
R-HSA-9606163 (Reactome) LYN and activated (phosphorylated) SYK phosphorylate BTK (Baba et al. 2001, Lin et al. 2009, also inferred from chicken homologs and mouse homologs) after BTK is recruited to the plasma membrane by phosphorylated BLNK (Baba et al. 2001) and phosphoinositol 3,4,5-trisphosphate (PIP3) (Salim et al. 1996). Phosphorylation of tyrosine-551 occurs within 30 seconds of B cell receptor activation and returns to low phosphorylation after 30 minutes (Nisitani et al. 1999).
R-HSA-9606883 (Reactome) In response to BCR activation, CD19 in a stable complex with VAV1 is phosphorylated by Src kinases (Chalupny et al. 1993, inferred from mouse homologs in Xu et al. 2002), one of which may be LYN (inferred from mouse homologs).
R-HSA-9606884 (Reactome) DAPP1 (BAM32) is recruited to the plasma membrane by the binding of its PH domain to phosphoinositol 3,4,5-trisphosphate (PIP3) (Dowler et al. 1999, Marshall et al. 2000, Ferguson et al. 2000). DAPP1 also binds phosphatidylinositol 3,4-bisphosphate (Dowler et al. 1999, Ferguson et al. 2000) and therefore remains bound at the plasma membrane after PIP3 has been dephosphorylated by phosphatases. At the plasma membrane DAPP1 is phosphorylated by a Src family kinase, likely LYN in B cells (Dowler et al. 2000).
R-HSA-9606887 (Reactome) Phosphorylated CD19 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 (PLCG2), which competes with VAV1 for the binding to phosphotyrosine-391 on CD19 (Brooks et al. 2000, Brooks et al. 2004). GRB2 appears to bind phosphotyrosine-330 on CD19 (Brooks et al. 2004).
R-HSA-9606894 (Reactome) Phosphorylated DAPP1 (BAM32) bound to phosphoinositol 3,4,5-trisphosphate (PIP3) at the plasma membrane binds phospholipase gamma-2 (PLCG2) (Marshall et al. 2000).
R-HSA-983696 (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).
R-HSA-983700 (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).
R-HSA-983703 (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).
R-HSA-983707 (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).
R-HSA-983709 (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).
RASGRP1,3R-HSA-1168374 (Reactome)
STIM1 DimerArrowR-HSA-1168376 (Reactome)
STIM1 DimerR-HSA-2089927 (Reactome)
STIM1 DimerR-HSA-434700 (Reactome)
STIM1:CalciumR-HSA-1168376 (Reactome)
STIM1:TRPC1ArrowR-HSA-2089927 (Reactome)
STIM1:TRPC1mim-catalysisR-HSA-2089943 (Reactome)
SYKR-HSA-983700 (Reactome)
TRPC1R-HSA-2089927 (Reactome)
UbR-HSA-1168643 (Reactome)
VAV1R-HSA-9606151 (Reactome)
p-4Y-PIK3AP1R-HSA-9606160 (Reactome)
p-BCL10R-HSA-1168644 (Reactome)
p-CARMA1 OligomerArrowR-HSA-1168635 (Reactome)
p-CARMA1 OligomerR-HSA-1168644 (Reactome)
p-CARMA1:MALT1:p-BCL10:TAK1:IKKArrowR-HSA-1168637 (Reactome)
p-CARMA1:MALT1:p-BCL10:TAK1:IKKR-HSA-1168641 (Reactome)
p-CARMA1:MALT1:p-BCL10:TAK1:IKKmim-catalysisR-HSA-1168641 (Reactome)
p-CARMA1:MALT1:p-BCL10:TAK1ArrowR-HSA-1168641 (Reactome)
p-CARMA1:MALT1:p-BCL10ArrowR-HSA-1168644 (Reactome)
p-CARMA1:MALT1:p-BCL10R-HSA-1168637 (Reactome)
p-CD19:VAV1ArrowR-HSA-9606883 (Reactome)
p-CD19:VAV1R-HSA-9606887 (Reactome)
p-RASGRP1,3:DAGArrowR-HSA-1168374 (Reactome)
p-RASGRP1,3:DAGmim-catalysisR-HSA-1168636 (Reactome)
p-Y139-DAPP1:PIP3ArrowR-HSA-9606884 (Reactome)
p-Y139-DAPP1:PIP3R-HSA-9606894 (Reactome)
p-Y139-DAPP1:PLCG2:PIP3ArrowR-HSA-9606894 (Reactome)
p-Y762,807,822-CD22:Antigen:p-BCRArrowR-HSA-5690702 (Reactome)
p-Y762,807,822-CD22:Antigen:p-BCRR-HSA-5690701 (Reactome)
p21 RAS:GDPR-HSA-1168636 (Reactome)
p21 RAS:GTPArrowR-HSA-1168636 (Reactome)
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