blk proto-oncogene protein; tyrosine-protein kinase BLK; B lymphocyte kinase; p55-BLK (BLK)
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Function
- non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation & signaling
- role in transmitting signals through surface immunoglobulins
- supports the pro-B to pre-B transition, as well as the signaling for growth arrest & apoptosis downstream of the B-cell recept
- specifically binds & phosphorylates CD79A at Tyr Y188 & Y199 as well as CD79B at Y196 & Y207
- phosphorylates immunoglobulin G receptors FCGR2A, FCGR2B & FCGR2C
- with FYN & LYN, plays a role in pre-B-cell receptor-mediated NF-kappa-B activation
- role in BTK activation by indirectly stimulating BTK autophosphorylation
- in pancreatic islets, acts as a modulator of beta-cells through up-regulation of PDX1 & NKX6-1 with stimulation of insulin secretion in response to glucose
- antibody-mediated surface engagement of the B-cell receptor which results in the phosphorylation of BLK on Tyr & stimulates enzymatic activity
- ubiquitination of activated BLK by the UBE3A ubiquitin protein ligase leads to its degradation by the ubiquitin- proteasome pathway (putative)
- interacts with CBL (via SH2 domain)
- interacts with CD79A & CD79B (via SH2 domain) (putative)
Structure
- belongs to the Tyr protein kinase family, SRC subfamily
- contains 1 protein kinase domain
- contains 1 SH2 domain
- contains 1 SH3 domain
Compartment
- cell membrane; lipid-anchor (putative)
- present & active in lipid rafts
- membrane location is required for the phosphorylation of CD79A & CD79B
Expression
- expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands & hair follicles
- expression is under the control of NF-kappa-B as well as the B-cell specific transcription factors PAX5 & EBF1
Pathology
- mutations in BLK are associated with maturity-onset diabetes of the young 11 (MODY11)
- genetic variation in the upstream region of the BLK gene & C8orf13 gene (chromosome 8p23.1) is associated with systemic lupus erythematosus
Genetics
- apparently linked with C8orf13 gene (chromosome 8p23.1)
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/P51451.html
- ↑ Bolen JB, Rowley RB, Spana C, Tsygankov AY. The Src family of tyrosine protein kinases in hemopoietic signal transduction. FASEB J. 1992 Dec;6(15):3403-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1281458
- ↑ Hom G, Graham RR, Modrek B et al Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med. 2008 Feb 28;358(9):900-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/1820409