B cell receptor signaling pathway (Homo sapiens)

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CHUKIKBKG1DAGCa2+Co-stimulatory regulationCalmodulinCalcineurinCYNUCYCYNUCYB cell receptor signaling pathwayNUNUNUCYILF2E2F3NFKB1PRELRELAPPRAF1PMAP3K7MEF2DIRF4HRASGTPCREB1MEF2CRAC2HCLS1CAMK2ABCAR1RELASH3BP2MAP2K6PVAV2CAMK2ARASGRP3NFATC2NFATC2PRKCDPBCL6NCK1PINPP5DGRB2VAV1RPS6KA1MYCAntigenMALT1CD79BNFATC3SYKPBRAFPCRKPLCG1SHC1AKT1PCD45FOXO1ELK1PTPN6GAB2PPIK3R1PTPN11PMAPK3PPIK3R1PPIK3R2PPIK3CGPPLCG2GAB1PMAPK14PMAP2K2PLYNPIK3AP1VAV1PETS1CD79AGSK3ACD19PLAT2RAC1RAPGEF1CD81GSK3BMAXBTKCDC42CBLPPLCG2PPDPK2PMAPK4MAPK8PMAPK9PBLNKPMYCBLKPRPS6KA1PPIP5K1APDPK1PTECCRKLPTPN18LCKPMAP2K1PFYNPMAPK1PJUNPIP5K1CPIP5K1BPRKCB1DAGIP3PI-4,5-P2PI-4-PBCL10CARD11PTPN6IKBKBPGTF2INFKBIAPMAPK9CD22ATF2GRB2SHC1SOS1CR2DAPP1MAP4K1NFATC3MAPK14MAPK8MAPK1MAPK3NFKB1RELNUCYNUCYProtein - protein dissociationReceptorProteinEnzyme complexmRNAProteinProteinLigandSmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMolecule


The functional B-cell receptor is a multi-protein complex consisting of an antigen binding subunit and a signaling subunit. The antigen binding subunit is the membrane bound immunoglobulin and the signaling subunit consists of the Igα and Igβ proteins, which are covalently bound to each other. Both Igα and Igβ proteins have an immunoreceptor tyrosine -based activation motif (ITAM) each in its cytoplasmic region, which is responsible for the initiation and propagation of signaling. Antigen binding to the immunoglubulin results in the aggregation of both the immunoglobulin and the Igα/β subunits. This results in the phosphorylation of the tyrosine residues in the ITAM motif of the Igα/β subunits by the src-family of protein tyrosine kinases Lyn and Syk. The Src family kinases are initially in the proximity of the BCR as a result of membrane anchoring by virtue of its their acetylation. The N-terminal region of the kinases can also interact with the non-phosphorylated ITAMs of Igα. This association is further enhanced upon BCR engagement as a result of accumulation in BCR containing lipid rafts and SH2 domain mediated binding to the phosphorylated tyrosine residues in ITAMs. This increased association helps in amplifying the BCR mediated signaling. Doubly phosphorylated Igα/β ITAMs are necessary for efficient recruitment of Syk and its activation. Activated Syk then phsophorylates the adapter molecule B cell linker protein (BLNK), which acts as molecular scaffold for the recruitment of multiple effectors and hence the propagation of multiple signaling pathways. BLNK binds to Btk and PLCγ2 which results in optimal phosphorylation and activation of PLC. This is an important mechanism which links BCR to Ca2+ signaling. Apart from the PLC mediated Ca2+ signaling, BCR triggering also results in the the activaion of phosphatidylinositol-3 kinase (PI-3K). This activation takes place through the recruitment of p85 adaptor subunit of PI-3K to CD19 co-receptor, which is phosphorylated by Lyn on its cytoplasmic Y-X-X-M motif. Alternatively, PI-3K can be recruited to the plasma membrane by other adapter molecules including PIK3AP, CBL or GAB1/2. PI-3K catalyzes the phosphorylation of phosphatidylinositol 4,5-bisphosphate to phosphatidyl inositol 3,4,5-bisphosphate. Akt, a serine threonine kinase, is recruited to the plasma membrane by virtue of its N-terminal PH-domain where it is activated by conformational changes and phosphorylation. Activated Akt phosphorylates several substrates resulting in diverse physiological consequences: Forkhead transcription factors - resulting in its degradation and hence inhibition of expression of pro-apoptotic genes, glycogen synthase kinase-3 GSK3 -leading to its inhibition and hence regulation of cell-cycle. The tanscription factor NF-kappaB is also found to be activated in BCR signaling in a Btk, PI-3K and PKC dependent manner.

BCR engagement can also result in the association of GRB2/SOS complex with either SHC or BLNK, which results in the activation of the Ras/Raf/MEK/ERK signaling cascade. This cascade leads to the activation of transcription factors including ELK and MYC. BCR activation also results in the activation of JNKs and p38MAPK.

Please access this pathway at NetSlim database.

If you use this pathway, please cite following paper: Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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  1. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK, Telikicherla D, Navarro JD, Mathivanan S, Pecquet C, Gollapudi SK, Tattikota SG, Mohan S, Padhukasahasram H, Subbannayya Y, Goel R, Jacob HK, Zhong J, Sekhar R, Nanjappa V, Balakrishnan L, Subbaiah R, Ramachandra YL, Rahiman BA, Prasad TS, Lin JX, Houtman JC, Desiderio S, Renauld JC, Constantinescu SN, Ohara O, Hirano T, Kubo M, Singh S, Khatri P, Draghici S, Bader GD, Sander C, Leonard WJ, Pandey A; ''NetPath: a public resource of curated signal transduction pathways.''; Genome Biol, 2010 PubMed Europe PMC Scholia


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120701view13:17, 23 December 2021EweitzStandardize font, weight, case
117659view11:52, 22 May 2021EweitzModified title
115881view12:33, 19 March 2021EgonwCopied the NetPath reference into the literature list
115879view12:30, 19 March 2021EgonwModified description
108321view20:51, 6 December 2019L DupuisConverted interactions to graphical lines in legend
106310view17:47, 20 August 2019KhanspersModified description
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89900view13:18, 6 October 2016MkutmonModified description
89899view13:17, 6 October 2016MkutmonModified description
79985view16:20, 29 April 2015Zariannotated PDPK2, CD79B ,CD79A, CD19 and LCK
78566view14:50, 7 January 2015MaintBotadded missing graphIds
72101view21:43, 24 October 2013Mkutmonadded datasource for "GSK3A" and "CD81"
71524view19:22, 17 October 2013MaintBotremoved data source from nodes without identifier
67071view10:02, 26 June 2013Christine ChichesterOntology Term : 'B cell receptor signaling pathway' added !
63145view20:12, 8 May 2013MaintBotUpdating GPML version
47980view14:44, 23 April 2012NetPathModified description
44975view14:24, 6 October 2011MartijnVanIerselOntology Term : 'signaling pathway pertinent to immunity' added !
44972view14:22, 6 October 2011MartijnVanIerselOntology Term : 'B cell' added !
44829view07:29, 6 October 2011Mkutmonconnected some lines
44620view17:50, 22 September 2011KhanspersUpdating content to NetSlim
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41190view23:43, 1 March 2011MaintBotRemoved redundant pathway information and comments
35652view21:44, 12 February 2010KhanspersModified description
20725view11:29, 14 November 2008MaintBot[[Pathway:Homo sapiens:B Cell Receptor NetPath 12]] moved to [[Pathway:WP23]]: Moved to stable identifier
7914view13:46, 7 January 2008MaintBot[[Pathway:Human:B Cell Receptor NetPath 12]] moved to [[Pathway:Homo sapiens:B Cell Receptor NetPath 12]]: Renaming species
7582view16:01, 18 December 2007MaintBotfixed category names
7201view12:33, 4 November 2007MaintBotAdded categories to GPML
6296view22:17, 22 May 2007A.Pandeygpml file for [[Human:B_Cell_Receptor_NetPath_12]]

External references


View all...
NameTypeDatabase referenceComment
AKT1Protein207 (Entrez Gene)
ATF2Protein1386 (Entrez Gene)
BCAR1Protein8462 (Entrez Gene)
BCL10Protein8915 (Entrez Gene)
BCL6Protein604 (Entrez Gene)
BLKProtein640 (Entrez Gene)
BLNKProtein29760 (Entrez Gene)
BRAFProtein673 (Entrez Gene)
BTKProtein695 (Entrez Gene)
CAMK2AProtein815 (Entrez Gene)
CARD11Protein84433 (Entrez Gene)
CBLProtein867 (Entrez Gene)
CD19Protein930 (Entrez Gene)
CD22Protein933 (Entrez Gene)
CD45Protein5788 (Entrez Gene)
CD79AProtein973 (Entrez Gene)
CD79BProtein974 (Entrez Gene)
CD81Protein975 (Entrez Gene)
CDC42Protein998 (Entrez Gene)
CHUKProtein1147 (Entrez Gene)
CR2Protein1380 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
CRKProtein1398 (Entrez Gene)
CRKLProtein1399 (Entrez Gene)
DAPP1Protein27071 (Entrez Gene)
E2F3Rna1871 (Entrez Gene)
ELK1Protein2002 (Entrez Gene)
ETS1Protein2113 (Entrez Gene)
FOXO1Protein2308 (Entrez Gene)
FYNProtein2534 (Entrez Gene)
GAB1Protein2549 (Entrez Gene)
GAB2Protein9846 (Entrez Gene)
GRB2Protein2885 (Entrez Gene)
GSK3AProtein2931 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
GTF2IProtein2969 (Entrez Gene)
HCLS1Protein3059 (Entrez Gene)
HRASProtein3265 (Entrez Gene)
IKBKBProtein3551 (Entrez Gene)
IKBKGProtein8517 (Entrez Gene)
ILF2Rna3608 (Entrez Gene)
INPP5DProtein3635 (Entrez Gene)
IRF4Rna3662 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
LAT2Protein7462 (Entrez Gene)
LCKProtein3932 (Entrez Gene)
LYNProtein4067 (Entrez Gene)
MALT1Protein10892 (Entrez Gene)
MAP2K1Protein5604 (Entrez Gene)
MAP2K2Protein5605 (Entrez Gene)
MAP2K6Protein5608 (Entrez Gene)
MAP3K7Protein6885 (Entrez Gene)
MAP4K1Protein11184 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5596 (Entrez Gene)
MAPK4Protein5596 (Entrez Gene)
MAPK8Protein5599 (Entrez Gene)
MAPK9Protein5601 (Entrez Gene)
MAXProtein4149 (Entrez Gene)
MEF2CRna4208 (Entrez Gene)
MEF2DRna4209 (Entrez Gene)
MYCRna4609 (Entrez Gene)
NCK1Protein4690 (Entrez Gene)
NFATC2Protein4773 (Entrez Gene)
NFATC3Protein4775 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene)
PDPK1Protein5170 (Entrez Gene)
PDPK2Protein653650 (Entrez Gene)
PI-4-PProtein5777 (Entrez Gene)
PIK3AP1Protein118788 (Entrez Gene)
PIK3CGProtein5294 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PIP5K1AProtein8394 (Entrez Gene)
PIP5K1BProtein8395 (Entrez Gene)
PIP5K1CProtein23396 (Entrez Gene)
PLCG1Protein5335 (Entrez Gene)
PLCG2Protein5336 (Entrez Gene)
PRKCB1Protein5579 (Entrez Gene)
PRKCDProtein5580 (Entrez Gene)
PTPN11Protein5781 (Entrez Gene)
PTPN18Protein26469 (Entrez Gene)
PTPN6Protein5777 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
RAC2Protein5880 (Entrez Gene)
RAF1Protein5894 (Entrez Gene)
RAPGEF1Protein2889 (Entrez Gene)
RASGRP3Protein25780 (Entrez Gene)
RELProtein5966 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RPS6KA1Protein6195 (Entrez Gene)
SH3BP2Protein6452 (Entrez Gene)
SHC1Protein6464 (Entrez Gene)
SOS1Protein6654 (Entrez Gene)
SYKProtein6850 (Entrez Gene)
TECProtein7006 (Entrez Gene)
VAV1Protein7409 (Entrez Gene)
VAV2Protein7410 (Entrez Gene)

Annotated Interactions

No annotated interactions

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