1blk

Structural highlights

Function

[BLK_MOUSE] Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at 'Tyr-188'and 'Tyr-199', as well as CD79B at 'Tyr-196' and 'Tyr-207'. Phosphorylates also the immunoglobulin G receptor FCGR2. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Contributes also to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Tyrosine kinase 3D structures

References

1. ↑ Dymecki SM, Niederhuber JE, Desiderio SV. Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells. Science. 1990 Jan 19;247(4940):332-6. PMID:2404338
2. ↑ Yao XR, Scott DW. Antisense oligodeoxynucleotides to the blk tyrosine kinase prevent anti-mu-chain-mediated growth inhibition and apoptosis in a B-cell lymphoma. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7946-50. PMID:7690139
3. ↑ Wasserman R, Li YS, Hardy RR. Differential expression of the blk and ret tyrosine kinases during B lineage development is dependent on Ig rearrangement. J Immunol. 1995 Jul 15;155(2):644-51. PMID:7608542
4. ↑ Saouaf SJ, Kut SA, Fargnoli J, Rowley RB, Bolen JB, Mahajan S. Reconstitution of the B cell antigen receptor signaling components in COS cells. J Biol Chem. 1995 Nov 10;270(45):27072-8. PMID:7592958
5. ↑ Mahajan S, Fargnoli J, Burkhardt AL, Kut SA, Saouaf SJ, Bolen JB. Src family protein tyrosine kinases induce autoactivation of Bruton's tyrosine kinase. Mol Cell Biol. 1995 Oct;15(10):5304-11. PMID:7565679
6. ↑ Saouaf SJ, Wolven A, Resh MD, Bolen JB. Palmitylation of Src family tyrosine kinases regulates functional interaction with a B cell substrate. Biochem Biophys Res Commun. 1997 May 19;234(2):325-9. PMID:9177269 doi:http://dx.doi.org/10.1006/bbrc.1997.6638
7. ↑ Malek SN, Dordai DI, Reim J, Dintzis H, Desiderio S. Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7351-6. PMID:9636152
8. ↑ Tretter T, Ross AE, Dordai DI, Desiderio S. Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk. J Exp Med. 2003 Dec 15;198(12):1863-73. Epub 2003 Dec 8. PMID:14662906 doi:http://dx.doi.org/10.1084/jem.20030729
9. ↑ Saijo K, Schmedt C, Su IH, Karasuyama H, Lowell CA, Reth M, Adachi T, Patke A, Santana A, Tarakhovsky A. Essential role of Src-family protein tyrosine kinases in NF-kappaB activation during B cell development. Nat Immunol. 2003 Mar;4(3):274-9. Epub 2003 Feb 3. PMID:12563261 doi:http://dx.doi.org/10.1038/ni893
10. ↑ Metzler WJ, Leiting B, Pryor K, Mueller L, Farmer BT 2nd. The three-dimensional solution structure of the SH2 domain from p55blk kinase. Biochemistry. 1996 May 21;35(20):6201-11. PMID:8639560 doi:10.1021/bi960157x