Study of B cell antigen receptor (BCR)-mediated signal transduction pathway

我们鉴定了一种新的BCR介导的信号转导的磷酸蛋白，它是与IGA(MB-1)共沉淀的分子。该克隆具有独特的结构，命名为Alpha4，是与MB-1蛋白相关的第四组分。酵母同系物(Tap42)是由另一个组分离的，是生长因子介导的雷帕霉素敏感途径信号转导的关键分子。Alpha4/Tap42目前被认为是雷帕霉素敏感途径的主要信号转导分子，可能通过激活S6激酶活性而导致蛋白质合成。我们制备了该基因敲除小鼠，发现Alpha4对生长尤其是胚胎发育是必不可少的。通过使用Cre-lox P系统的条件性靶向策略，我们可以删除X染色体上的alpha4基因，并表明alpha4对BCR交联物刺激的成熟B细胞的生长也是必不可少的。在这里，我们可以清楚地证明，Alpha4参与了BCR介导的雷帕霉素敏感性的信号转导，从而促进了蛋白质的合成。我们将进一步研究Alpha4相关途径在免疫系统中的生物学功能。

We identified a novel phosphoprotein of BCR mediated signal transduction as a coprecipitated molecule with Iga (MB-1). The cDNA clone showed a unique structure and named it alpha4 as a fourth component associated with MB-1 protein. The yeast homologue (Tap42) was isolated by the other group and was found to be a critical molecule of the growth factor mediated signal transduction of rapamycin-sensitive pathway. The alpha4/Tap42 is now known as a major signal transduction molecule of rapamycin sensitive pathway leading to protein synthesis probably through the activation of S6 kinase activity.We prepared the gene knock out mice and found that the alpha4 is essential for the growth especially at the embryonal development. By the conditional targeting strategy using Cre-lox P system we could delete the alpha4 locus on the X chromosome and show that alpha4 is also essential for the growth of mature B cells stimulated with BCR crosslinking. Here, we could clearly demonstrate that alpha4 is involved in the BCR-mediated signal transduction of rapamycin sensitivity for the protein synthesis. We will further study the biological function of alpha4 related pathway in the immune system.