B cell receptor signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

B cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor (BCR) is an integral membrane protein complex that is composed of two immunoglobulin (Ig) heavy chains, two Ig light chains and two heterodimers of Ig-alpha and Ig-beta. After BCR ligation by antigen, three main protein tyrosine kinases (PTKs) -the SRC-family kinase LYN, SYK and the TEC-family kinase BTK- are activated. Phosphatidylinositol 3-kinase (PI3K) and phospholipase C-gamma 2 (PLC-gamma 2) are important downstream effectors of BCR signalling. This signalling ultimately results in the expression of immediate early genes that further activate the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes.    
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B cell receptor signaling pathway - Homo sapiens (human) cluster_Membrane Membrane Antigen breakpoint cluster region BCR Antigen->BCR node3 Co-stimulator CD19 molecule CD19 node3->CD19 node4 Co-inhibitor 1 CD22 molecule CD22 node4->CD22 CD72 molecule CD72 node4->CD72 node1 PIR-B node4->node1 node5 Co-inhibitor 2 Fc fragment of IgG,low affinity IIb,receptor (CD32) FCGR2B node5->FCGR2B Complement and Coagulation Cascade CD21 Complement and Coagulation Cascade->CD21 SHP1 spleen tyrosine kinase SYK SHP1->SYK -p Bruton agammaglobulinemia tyrosine kinase BTK SHP1->BTK -p B-cell linker BLNK SYK->BLNK +p node8 PLC-y2 SYK->node8 +p BCAP SYK->BCAP +p v-yes-1 Yamaguchi sarcoma viral related oncogene homolog LYN LYN->SYK +p LYN->BTK +p Bam32 LYN->Bam32 +p LYN->CD19 +p node2 Ig Alpha Ig Beta LYN->node2 +p BTK->BLNK BTK->node8 +p Rac Bam32->Rac node6 1 BLNK->node6 BLNK node7 VAV (1) BLNK->node7 ? BLNK->node8 growth factor receptor-bound protein 2 GRB2 BLNK->GRB2 node7->Rac Regulation of actin cytoskeleton Rac->Regulation of actin cytoskeleton IP3 node8->IP3 DAG node8->DAG node18 CA2+ Calcium signaling pathway IP3->node18 node9 VAV (2) SHIP PIP3 SHIP->PIP3 -p node10 12 PI3K PI3K->node10 PI3K PI3K->PIP3 BCAP->PI3K SOS GRB2->SOS node11 2 SOS->node11 SOS RAS guanyl releasing protein 3 (calcium and DAG-regulated) RASGRP3 SOS->RASGRP3 Ras RASGRP3->Ras DAG->RASGRP3 PKCBeta DAG->PKCBeta node12 3 PIP3->node12 PIP3 AKT PIP3->AKT node21 CALMA1 BCL10 MALT1 PKCBeta->node21 +p node13 1 Ras->node13 Ras Raf Ras->Raf node14 4 Raf->node14 Raf node16 MEK1/2 Raf->node16 +p node15 2 node16->node15 MEK1/2 Erk node16->Erk +p node17 24 Erk->node17 Erk AP1 Erk->AP1 +p CaN node18->CaN node19 29 AKT->node19 AKT glycogen synthase kinase 3 beta GSK3B AKT->GSK3B +p node23 IKKa IKKy IKKB AKT->node23 +p Survival node20 5 GSK3B->node20 GSK3B node21->node23 +u node22 7 node23->node22 IKKa~IKKy~IKKB IkB node23->IkB +p node24 3 AP1->node24 AP1 DNA 2 AP1->DNA 2 NFAT CaN->NFAT -p node25 2 NFAT->node25 NFAT DNA 1 NFAT->DNA 1 node26 32 NFkB NFkB->node26 NFkB DNA 3 NFkB->DNA 3 node27 4 IkB->NFkB IkB->node27 IkB Ubiquitin mediated proteolysis IkB->Ubiquitin mediated proteolysis node28 1 DNA 1->node28 DNA 2->node28 DNA 3->node28 B cell ontogeny node28->B cell ontogeny Autoimmunity node28->Autoimmunity Anergy node28->Anergy Immuno response node28->Immuno response node29 Antibody (Ig) production node28->node29 node30 Germinal center (GC) formation node28->node30 BCR->LYN CD19->node9 CD19->PI3K CD22->SHP1 CD72->SHP1 node1->SHP1 FCGR2B->SHIP CD81 molecule CD81 LEU13 print "