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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 当免疫细胞识别到病原体的存在时，它们会收到使细胞对病原体做出反应的信号。我们正在研究一种名为T细胞的免疫细胞的信号通路。为了让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CD28。尽管目前尚不清楚激活T细胞需要来自两个受体的信号，但信号协调的机制仍不清楚。本研究项目的目的是研究TCR和CD28启动的信号通路如何结合在一起导致T细胞的激活。我们的研究重点是GADS接头蛋白，这是一种最佳TCR介导信号所需的信号蛋白。我们之前建立了GADS缺陷小鼠系，发现GADS在T细胞发育的几个阶段都是必需的。将我们的小鼠品系与文献中描述CD28-/-小鼠的报告进行比较，我们发现了惊人的相似表型。这导致了一种假设，即Gads可能调节CD28介导的信号。具体地说，我们假设Gads、CD28和Akt在一个共同的信号通路中相连。在这项提案中，我们正在使用生化和遗传技术来研究Gads是否可以调节CD28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.