B cell receptor signaling pathway (Bos taurus)

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CHUKIKBKGDAGCo-stimulatory regulationCa2+CalmodulinCalcineurinCYNUCYCYNUCYB Cell Receptor Signaling PathwayNUNUNUCYNFKB1ILF2E2F3PRELRELAPPRAF1PMAP3K7MEF2DIRF4HRASGTPCREB1MEF2CRAC2HCLS1CAMK2ATIEG2RELASH3BP2MAP2K6PVAV2CAMK2ARASGRP3NFATC2NFATC2PRKCDPBCL6NCK1PINPP5DGRB2VAV1RPS6KA1MYCAntigenMALT1CD79BNFATC3SYKPBRAFPCRKPLCG1SHC1AKT1PPTPRCFOXO1ELK1PTPN6GAB2PPIK3R1PTPN11PMAPK4PPIK3R1PPIK3R2PPIK3CGPPLCG2GAB1PMAPK14PMAP2K2PLYNPIK3AP1VAV1PETS1CD79AGSK3ACD19PLAT2RAC1RAPGEF1CD81GSK3BMAXBTKCDC42CBLPPLCG2PPDPK2PMAPK4MAPK8PMAPK9PBLNKPMYCBLKPRPS6KA1PPIP5K1APDPK1PTECCRKLPTPN18LCKPMAP2K1PFYNPMAPK1PJUNPIP5K1CPIP5K1BPRKCBDAGIP3PI-4,5-P2PTPN6BCL10CARD11PTPN6IKBKBPGTF2IBIKBAPMAPK9CD22ATF2GRB2SHC1SOS1CR2DAPP1MAP4K1NFATC3MAPK14MAPK8MAPK1MAPK4NFKB1RELNUCYNUCYProtein - 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


Description

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 Igإ’آ± and Igإ’≤ proteins, which are covalently bound to each other. Both Igإ’آ± and Igإ’≤ 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 Igإ’آ±/إ’≤ subunits. This results in the phosphorylation of the tyrosine residues in the ITAM motif of the Igإ’آ±/إ’≤ 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 Igإ’آ±. 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 Igإ’آ±/إ’≤ 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 PLCإ’≥2 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, you must 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.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP23(79985) with a 94.0% conversion rate.

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Bibliography

  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

History

View all...
CompareRevisionActionTimeUserComment
117479view10:59, 21 May 2021EweitzModified title
115959view08:25, 22 March 2021EgonwCopied the NetPath paper into the literature list
115949view07:12, 22 March 2021EgonwModified description
89901view13:19, 6 October 2016MkutmonModified description
80807view15:26, 30 June 2015Mkutmonhomology conversion
67068view10:02, 26 June 2013Christine ChichesterOntology Term : 'B cell receptor signaling pathway' added !
63478view17:22, 10 May 2013MaintBotupdating gpml
40541view19:30, 1 March 2011MaintBotRemoved redundant pathway information and comments
35705view23:14, 12 February 2010AlexanderPico
33782view00:09, 9 December 2009MaintBotAutomatic update of empty xrefs
32499view12:48, 17 August 2009MaintBotFixed text labels
31197view19:32, 13 August 2009MaintBotFixed text labels
30594view22:13, 29 July 2009MaintBotNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
ATF2ProteinENSBTAG00000002295 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1386
BCL10ProteinENSBTAG00000013851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8915
BCL6ProteinENSBTAG00000001511 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:604
BIKBAProteinENSBTAG00000016683 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
BLKProteinENSBTAG00000005049 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:640
BLNKProteinENSBTAG00000021358 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:29760
BRAFProteinENSBTAG00000021761 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:673
BTKProteinENSBTAG00000019250 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:695
CAMK2AProteinENSBTAG00000020087 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:815
CARD11ProteinENSBTAG00000014698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:84433
CBLProteinENSBTAG00000006817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:867
CD19ProteinENSBTAG00000032122 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:930
CD22ProteinENSBTAG00000011887 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:933
CD79AProteinENSBTAG00000001882 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:973
CD79BProteinENSBTAG00000044204 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:974
CD81ProteinENSBTAG00000047495 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:975
CDC42ProteinENSBTAG00000001700 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:998
CHUKProteinENSBTAG00000007591 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
CR2Protein
CREB1ProteinENSBTAG00000005474 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
CRKProteinENSBTAG00000005665 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1398
CRKLProteinENSBTAG00000045548 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1399
DAGProtein
DAPP1ProteinENSBTAG00000007921 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:27071
E2F3RnaENSBTAG00000021045 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1871
ELK1ProteinENSBTAG00000015817 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2002
ETS1ProteinENSBTAG00000002341 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2113
FOXO1ProteinENSBTAG00000044105 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2308
FYNProteinENSBTAG00000011851 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
GAB1ProteinENSBTAG00000002813 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2549
GAB2Protein
GRB2ProteinENSBTAG00000004736 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
GSK3AProteinENSBTAG00000020756 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2931
GSK3BProteinENSBTAG00000048057 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
GTF2IProteinENSBTAG00000009780 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2969
HCLS1ProteinENSBTAG00000001009 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3059
HRASProteinENSBTAG00000046644 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
IKBKBProteinENSBTAG00000007599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IKBKGProteinENSBTAG00000006268 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8517
ILF2RnaENSBTAG00000012471 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3608
INPP5DProteinENSBTAG00000020173 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3635
IP3Protein
IRF4RnaENSBTAG00000002929 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3662
JUNProteinENSBTAG00000004037 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
LAT2ProteinENSBTAG00000045767 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7462
LCKProteinENSBTAG00000012695 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3932
LYNProteinENSBTAG00000020034 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4067
MALT1ProteinENSBTAG00000027916 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10892
MAP2K1ProteinENSBTAG00000033983 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
MAP2K2ProteinENSBTAG00000024450 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAP2K6ProteinENSBTAG00000001609 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5608
MAP3K7ProteinENSBTAG00000002625 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
MAP4K1ProteinENSBTAG00000021145 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:11184
MAPK14ProteinENSBTAG00000020783 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK4ProteinENSBTAG00000009907 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5596
MAPK8ProteinENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK9ProteinENSBTAG00000004709 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
MAXProteinENSBTAG00000017994 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4149
MEF2CRnaENSBTAG00000020701 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4208
MEF2DRnaENSBTAG00000046545 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4209
MYCRnaENSBTAG00000008409 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4609
NCK1ProteinENSBTAG00000018427 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4690
NFATC2ProteinENSBTAG00000018270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4773
NFATC3ProteinENSBTAG00000004368 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4775
NFKB1ProteinENSBTAG00000020270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
PDPK1ProteinENSBTAG00000034436 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5170
PDPK2Protein
PI-4,5-P2Protein
PIK3AP1ProteinENSBTAG00000019872 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:118788
PIK3CGProteinENSBTAG00000020848 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5294
PIK3R1ProteinENSBTAG00000010989 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
PIK3R2ProteinHomologyConvert: Multiple homologues found: En:ENSBTAG00000002350;En:ENSBTAG00000002350;
PIP5K1AProteinENSBTAG00000006099 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8394
PIP5K1BProteinENSBTAG00000009917 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8395
PIP5K1CProteinENSBTAG00000000710 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23396
PLCG1ProteinENSBTAG00000017584 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5335
PLCG2ProteinENSBTAG00000002103 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5336
PRKCBProteinENSBTAG00000020921 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5579
PRKCDProteinENSBTAG00000008719 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
PTPN11ProteinENSBTAG00000002048 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
PTPN18ProteinENSBTAG00000011658 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:26469
PTPN6ProteinENSBTAG00000020294 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5777
PTPRCProteinENSBTAG00000023144 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5788
RAC1ProteinENSBTAG00000009233 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
RAC2ProteinENSBTAG00000011043 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5880
RAF1ProteinENSBTAG00000045748 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
RAPGEF1ProteinENSBTAG00000020791 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2889
RASGRP3ProteinENSBTAG00000008006 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25780
RELAProteinENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RELProteinENSBTAG00000015386 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5966
RPS6KA1ProteinENSBTAG00000014447 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6195
SH3BP2ProteinENSBTAG00000013996 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6452
SHC1ProteinENSBTAG00000019838 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
SOS1ProteinENSBTAG00000011643 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6654
SYKProteinENSBTAG00000004767 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6850
TECProteinENSBTAG00000005062 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7006
TIEG2ProteinENSBTAG00000046218 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8462
VAV1ProteinENSBTAG00000039160 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7409
VAV2ProteinENSBTAG00000004511 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7410

Annotated Interactions

No annotated interactions
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