Isoform-dependent interaction of BRDG1 with Tec kinase.
Tec is the prototype of an emerging family of protein-tyrosine kinases. Tec and Btk, another member of this family, together participate in the development of B-cell immune system. We previously identified one of the downstream messengers for human Tec kinase, BRDG1. BRDG1 is associated with Tec and becomes tyrosine-phosphorylated in B-cells by the engagement of B-cell antigen receptor (BCR). Here we show that overexpression of BRDG1 strongly augments BCR- mediated activation of cAMP-response element binding protein ( CREB) but not that of c-Jun and the promoters of c-MYC and BCL-xL genes. Furthermore, we isolated the murine orthologue of BRDG1. Three isoforms of BRDG1 are generated by alternative splicing of the message. Two of them have a deletion of 33 amino acids in a Pleckstrin homology (PH) domain of BRDG1. Both the tyrosine-phosphorylation and CREB- activating ability of BRDG1 were isoform-dependent, suggesting a role of the PH domain of BRDG1. These data have identified a novel regulatory mechanism of CREB family of transcriptional factors.[1]References
- Isoform-dependent interaction of BRDG1 with Tec kinase. Yokohari, K., Yamashita, Y., Okada, S., Ohya, K., Oda, S., Hatano, M., Mano, H., Hirasawa, H., Tokuhisa, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
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