Yokohari K, Yamashita Y, Okada S, Ohya K, Oda S, Hatano M, Mano H, Hirasawa H, Tokuhisa T
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan.
Biochem Biophys Res Commun. 2001 Nov 30;289(2):414-20. doi: 10.1006/bbrc.2001.6008.
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.
Tec是一个新出现的蛋白酪氨酸激酶家族的原型。Tec和该家族的另一个成员Btk共同参与B细胞免疫系统的发育。我们之前鉴定出人类Tec激酶的一个下游信使分子BRDG1。BRDG1与Tec相关联，并在B细胞中通过B细胞抗原受体（BCR）的激活而发生酪氨酸磷酸化。在此我们表明，BRDG1的过表达强烈增强BCR介导的环磷酸腺苷反应元件结合蛋白（CREB）的激活，但不增强c-Jun以及c-MYC和BCL-xL基因启动子的激活。此外，我们分离出了BRDG1的小鼠同源物。BRDG1的三种异构体是通过该信使RNA的可变剪接产生的。其中两种在BRDG1的普列克底物蛋白同源（PH）结构域中缺失了33个氨基酸。BRDG1的酪氨酸磷酸化和CREB激活能力均依赖于异构体，这表明BRDG1的PH结构域具有作用。这些数据确定了转录因子CREB家族的一种新的调控机制。
