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

我们发现了一种新的BCR介导信号转导的磷酸化蛋白，它与Iga （MB-1）共沉淀。cDNA克隆显示出独特的结构，并将其命名为alpha4，作为MB-1蛋白的第四个相关成分。另一组分离到酵母同源物（Tap42），发现它是雷帕霉素敏感通路中生长因子介导的信号转导的关键分子。alpha4/Tap42是目前已知的雷帕霉素敏感通路的主要信号转导分子，可能通过激活S6激酶活性导致蛋白质合成。我们对小鼠进行基因敲除，发现α - 4基因在小鼠的生长，尤其是胚胎发育中起着至关重要的作用。通过使用Cre-lox P系统的条件靶向策略，我们可以删除X染色体上的alpha4位点，并表明alpha4对于BCR交联刺激的成熟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信号转导的蛋白质合成。我们将进一步研究alpha4相关通路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.