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)

external resources
NCBI:1269183
REACTOME:R-HSA-983705
PUBMED:1702903
PUBMED:2011584
PUBMED:1081164
PUBMED:19065780
PUBMED:16849466
PUBMED:1375264
PUBMED:7538118
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PUBMED:19249086
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PUBMED:10648173
PUBMED:4589993
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PUBMED:1376928
PUBMED:7688784
PUBMED:6335036
PUBMED:17052215
PUBMED:18818202
PUBMED:20206686
PUBMED:7592958
PUBMED:7524079
PUBMED:15489917
PUBMED:15509800
PUBMED:18187424
PUBMED:7927516
PUBMED:803528
PUBMED:19909372
PUBMED:20192804
PUBMED:8306975

genes
AKT1 , AKT2 , BAD , BLK , BTC , BTK , CALM1 , CALM2 , CALM3 , CASP9 , CBL , CBLB , CD19 , CD22 , CD28 , CD80 , CD86 , CD79A , CD79B , CDKN1A , CDKN1B , CHUK , CREB1 , HBEGF , EGF , EGFR , ERBB2 , ERBB3 , ERBB4 , EREG , FGF1 , FGF2 , FGF3 , FGF4 , FGF5 , FGF6 , FGF7 , FGF8 , FGF9 , FGF10 , FGFR1 , FGFR3 , FGFR2 , FGFR4 , FOXO1 , FOXO3 , MTOR , FYN , GAB1 , GRB2 , GSK3A , GSK3B , HGF , NRG1 , NR4A1 , HRAS , IGLC1 , IGLC6 , IKBKB , INS , INSR , IRS1 , ITPR1 , ITPR2 , ITPR3 , KIT , KRAS , LCK , LYN , MDM2 , MET , KITLG , FOXO4 , MOV10 , NCK1 , NFKB1 , NFKBIA , NFKBIB , NFKBIE , NRAS , PDGFA , PDGFB , PDGFRA , PDGFRB , PDPK1 , PIK3CA , PIK3CB , PIK3CD , PIK3R1 , PIK3R2 , PIP4K2A , PLCG1 , PLCG2 , PPP2CA , PPP2CB , PPP2R1A , PPP2R1B , PPP2R5A , PPP2R5B , PPP2R5C , PPP2R5D , PPP2R5E , PRKCB , MAPK1 , MAPK3 , PSMA1 , PSMA2 , PSMA3 , PSMA4 , PSMA5 , PSMA6 , PSMA7 , PSMB1 , PSMB2 , PSMB3 , PSMB4 , PSMB5 , PSMB6 , PSMB7 , PSMB8 , PSMB9 , PSMB10 , PSMC1 , PSMC2 , PSMC3 , PSMC4 , PSMC5 , PSMC6 , PSMD1 , PSMD2 , PSMD3 , PSMD4 , PSMD5 , PSMD7 , PSMD8 , PSMD9 , PSMD10 , PSMD11 , PSMD12 , PSMD13 , PSME1 , PSME2 , PTEN , PTPN6 , PTPN11 , REL , RELA , RPS6KB2 , RPS27A , SHC1 , SKP1 , SOS1 , SRC , SRMS , STIM1 , SYK , MAP3K7 , TP53 , TRPC1 , TSC2 , UBA52 , UBB , UBC , VAV1 , SEM1 , FGF23 , PIP5K1A , PIP5K1B , PIP4K2B , CUL1 , PIK3R3 , IKBKG , IRS2 , FGF18 , FGF17 , FGF16 , IER3 , BCL10 , BTRC , KL , PSMF1 , NRG2 , PSMD6 , FGF19 , AKT3 , RASGRP1 , PSME3 , PSMD14 , NRG3 , AHCYL1 , FRS2 , MALT1 , PHLPP2 , TNRC6B , PSME4 , PHLPP1 , FBXW11 , PIP5K1C , RASGRP3 , FGF20 , AGO1 , FGF22 , DAPP1 , AGO2 , TNRC6A , IGKV3D-11 , IGKV5-2 , IGKV4-1 , BLNK , ICOS , SH3KBP1 , TRAT1 , PRR5 , TNRC6C , TRIB3 , MLST8 , MAPKAP1 , PIP4K2C , ORAI2 , AKT1S1 , CARD11 , ORAI1 , THEM4 , PIK3AP1 , PSMB11 , PSMA8 , NRG4 , KLB , AGO3 , AGO4 , RICTOR , C7orf76 , LOC100506136 , MIR4687 , MIR5196 ,