THE ROLE OF THE GADS ADAPTOR PROTEIN IN CD28-MEDIATED IMMUNITY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 当免疫细胞识别出病原体的存在时，它们会接收信号，导致细胞对病原体做出反应。 我们正在研究一种称为T细胞的免疫细胞中的信号通路。 为了使T细胞对病原体做出反应，它必须接收来自两个受体的信号：T细胞受体（TCR）和辅助受体（如CD 28）。 虽然目前尚不清楚激活T细胞需要来自两种受体的信号，但这些信号协调的机制仍不清楚。 该研究项目的目标是研究TCR和CD 28联合收割机启动的信号通路如何结合导致T细胞的活化。 我们的研究集中在Gads衔接蛋白，一种最佳TCR介导的信号传导所需的信号蛋白。 我们先前产生了Gads缺陷小鼠系，并发现Gads是T细胞发育过程中几个阶段所需的。 将我们的小鼠系与文献中描述的CD 28-/-小鼠进行比较，我们发现了惊人相似的表型。 这导致了Gads可能调节CD 28介导的信号传导的假设。 具体来说，我们假设Gads、CD 28和Akt在共同的信号通路中相互联系。 在这个提议中，我们使用生物化学和遗传学技术来研究Gads是否可以调节CD 28介导的Akt磷酸化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. When immune cells recognize the presence of a pathogen, they receive signals that cause the cell to respond to the pathogen. We are studying the signaling pathways in one type of immune cells called T cells. In order for a T cell to respond to a pathogen, it must receive signals from two receptors: the T cell receptor (TCR) and a co-receptor such as CD28. Although it is unknown that signals from two receptors are required to activate T cells, the mechanisms by which the signals are coordinated remain unclear. The goal of this research project is to examine how the signaling pathways initiated by the TCR and CD28 combine to result in the activation of T cells. Our research has focused on the Gads adaptor protein, a signaling protein required for optimal TCR-mediated signaling. We previously generated a Gads-deficient mouse line and found that Gads is required for several stages during T cell development. Comparing our mouse line to reports in the literature describing CD28-/- mice, we found strikingly similar phenotypes. This led to the hypothesis that Gads might regulate CD28-mediated signaling. Specifically, we hypothesize that Gads, CD28, and Akt are linked in a common signaling pathway. In this proposal, we are using biochemical and genetic techniques to investigate whether Gads can regulate CD28-mediated Akt phosphorylation.