Isoform-dependent interaction of BRDG1 with Tec kinase

Tee is the prototype of an emerging family of protein-tyrosine kinases. Tec and Btk, another member of this family, together participate in the develo pment of B-cell immune system. We previously identified one of the downstre am messengers for human Tec kinase, BRDG1. BRDG1 is associated with Tec and becomes tyrosine-phosphorylated in B-cells by the engagement of B-cell ant igen receptor (BCR). Here we show that overexpression of BRDG1 strongly aug ments BCR-mediated activation of cAMP-response element binding protein (CRE B) but not that of c-Jun and the promoters of c-MYC and BCL-xL genes. Furth ermore, we isolated the murine orthologue of BRDG1. Three isoforms of BRDG1 are generated by alternative splicing of the message. Two of them have a d eletion of 33 amino acids in a Pleckstrin homology (PH) domain of BRDG1. Bo th the tyrosine-phosphorylation and CREB-activating ability of BRDG1 were i soform-dependent, suggesting a role of the PH domain of BRDG1. These data h ave identified a novel regulatory mechanism of CREB family of transcription al factors. (C) 2001 Elsevier Science