KEGG   PATHWAY: hsa04662Help
Entry
hsa04662                    Pathway                                

Name
B cell receptor signaling pathway - Homo sapiens (human)
Description
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.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
B cell receptor signaling pathway
hsa04662

All organismsOrtholog table
Disease
H00540  
Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00645  
Incontinentia pigmenti
H00882  
Cocoon syndrome
H01387  
Activated PI3K-delta syndrome (APDS)
Drug
D03066  
Bectumomab (USAN/INN)
D04036  
Epratuzumab (USAN/INN)
D06348  
Yttrium Y 90 epratuzumab (USAN)
D06349  
Yttrium Y 90 epratuzumab tetraxetan (USAN)
D08933  
Inotuzumab ozogamicin (USAN/INN)
D09325  
Blinatumomab (USAN/INN)
D09347  
Fostamatinib (USAN)
D09348  
Fostamatinib disodium (USAN)
D09932  
Moxetumomab pasudotox (USAN/INN)
D10223  
Ibrutinib (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
973  
CD79A; CD79a molecule, immunoglobulin-associated alpha [KO:K06506]
974  
CD79B; CD79b molecule, immunoglobulin-associated beta [KO:K06507]
4067  
LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
6850  
SYK; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
695  
BTK; Bruton agammaglobulinemia tyrosine kinase [KO:K07370] [EC:2.7.10.2]
27071  
DAPP1; dual adaptor of phosphotyrosine and 3-phosphoinositides [KO:K12229]
29760  
BLNK; B-cell linker [KO:K07371]
10451  
VAV3; vav 3 guanine nucleotide exchange factor [KO:K05730]
7409  
VAV1; vav 1 guanine nucleotide exchange factor [KO:K05730]
7410  
VAV2; vav 2 guanine nucleotide exchange factor [KO:K05730]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5880  
RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
5881  
RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
5336  
PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
5530  
PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
4772  
NFATC1; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 [KO:K04446]
4773  
NFATC2; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 [KO:K17332]
4775  
NFATC3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 [KO:K17333]
2885  
GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654  
SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655  
SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
25780  
RASGRP3; RAS guanyl releasing protein 3 (calcium and DAG-regulated) [KO:K12362]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2353  
FOS; FBJ murine osteosarcoma viral oncogene homolog [KO:K04379]
3725  
JUN; jun proto-oncogene [KO:K04448]
84433  
CARD11; caspase recruitment domain family, member 11 [KO:K07367]
8915  
BCL10; B-cell CLL/lymphoma 10 [KO:K07368]
10892  
MALT1; mucosa associated lymphoid tissue lymphoma translocation gene 1 [KO:K07369] [EC:3.4.22.-]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4793  
NFKBIB; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
4794  
NFKBIE; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon [KO:K05872]
975  
CD81; CD81 molecule [KO:K06508]
930  
CD19; CD19 molecule [KO:K06465]
1380  
CR2; complement component (3d/Epstein Barr virus) receptor 2 [KO:K04012]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
3635  
INPP5D; inositol polyphosphate-5-phosphatase, 145kDa [KO:K03084] [EC:3.1.3.86]
3636  
INPPL1; inositol polyphosphate phosphatase-like 1 [KO:K15909] [EC:3.1.3.86]
933  
CD22; CD22 molecule [KO:K06467]
971  
CD72; CD72 molecule [KO:K06504]
5777  
PTPN6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
118788  
PIK3AP1; phosphoinositide-3-kinase adaptor protein 1 [KO:K12230]
11025  
LILRB3; leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 3 [KO:K06512]
2213  
FCGR2B; Fc fragment of IgG, low affinity IIb, receptor (CD32) [KO:K12560]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
8519  
IFITM1; interferon induced transmembrane protein 1 [KO:K06566]
Compound
C00076  
Calcium cation
C00165  
Diacylglycerol
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C05981  
Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Niiro H, Clark EA.
  Title
Regulation of B-cell fate by antigen-receptor signals.
  Journal
Nat Rev Immunol 2:945-56 (2002)
Reference
  Authors
Kurosaki T.
  Title
Genetic analysis of B cell antigen receptor signaling.
  Journal
Annu Rev Immunol 17:555-92 (1999)
Reference
  Authors
Nitschke L.
  Title
The role of CD22 and other inhibitory co-receptors in B-cell activation.
  Journal
Curr Opin Immunol 17:290-7 (2005)
Reference
  Authors
Morgan BP, Marchbank KJ, Longhi MP, Harris CL, Gallimore AM.
  Title
Complement: central to innate immunity and bridging to adaptive responses.
  Journal
Immunol Lett 97:171-9 (2005)
Reference
  Authors
Kurosaki T.
  Title
Regulation of B-cell signal transduction by adaptor proteins.
  Journal
Nat Rev Immunol 2:354-63 (2002)
Reference
  Authors
Nitschke L, Tsubata T.
  Title
Molecular interactions regulate BCR signal inhibition by CD22 and CD72.
  Journal
Trends Immunol 25:543-50 (2004)
Reference
  Authors
Jumaa H, Hendriks RW, Reth M.
  Title
B cell signaling and tumorigenesis.
  Journal
Annu Rev Immunol 23:415-45 (2005)
Reference
  Authors
Rickert RC.
  Title
Regulation of B lymphocyte activation by complement C3 and the B cell coreceptor complex.
  Journal
Curr Opin Immunol 17:237-43 (2005)
Reference
  Authors
Zouali M, Sarmay G
  Title
B lymphocyte signaling pathways in systemic autoimmunity: implications for pathogenesis and treatment.
  Journal
Arthritis Rheum 50:2730-41 (2004)
Reference
  Authors
Chiles TC.
  Title
Regulation and function of cyclin D2 in B lymphocyte subsets.
  Journal
J Immunol 173:2901-7 (2004)
Reference
  Authors
Allam A, Marshall AJ
  Title
Role of the adaptor proteins Bam32, TAPP1 and TAPP2 in lymphocyte activation.
  Journal
Immunol Lett 97:7-17 (2005)
Reference
  Authors
Gold MR
  Title
To make antibodies or not: signaling by the B-cell antigen receptor.
  Journal
Trends Pharmacol Sci 23:316-24 (2002)
Reference
PMID:9697839
  Authors
Fu C, Turck CW, Kurosaki T, Chan AC
  Title
BLNK: a central linker protein in B cell activation.
  Journal
Immunity 9:93-103 (1998)
Reference
  Authors
Okada T, Maeda A, Iwamatsu A, Gotoh K, Kurosaki T
  Title
BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation.
  Journal
Immunity 13:817-27 (2000)
Reference
  Authors
Shinohara H, Maeda S, Watarai H, Kurosaki T
  Title
IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells.
  Journal
J Exp Med 204:3285-93 (2007)
KO pathway
 

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