Adaptor molecules in lymphocyte signaling

超出提供的空间。T细胞和B细胞上抗原受体的结合导致一系列信号级联反应的激活，包括细胞蛋白的磷酸化、Ras-MAPK通路和钙离子通量的激活。在T细胞中，膜相关接头分子LAT通过将Grb2、Gads和PLC-y1募集到膜上，在连接TCR与Ras-MAPK激活和钙离子通量方面起着至关重要的作用。然而，目前还不清楚BCR参与如何与RAS-MAPK激活和钙通量相关联。在B细胞中还没有发现LAT样分子。最近，我们克隆了一个编码膜相关接头蛋白的新基因。我们将这个基因命名为Lab(激活B细胞的连接物)。我们的初步数据显示，LAB与LAT有许多相似之处。我们假设，在B细胞中，LAB通过将Grb2招募到膜上，将BCR参与与下游的Ras-MAPK激活和钙离子通量偶联。本研究旨在进一步研究LAB在B细胞活化和发育中的作用。为了检验这一假说，我们设计了三个具体目标。在特定目的1中，LAB基因将在鸡DT40B细胞系中被打乱。由该基因缺失引起的信号缺陷将被描述。在特定的目标2中，我们将使用转基因小鼠来检验LAT和LAT之间的功能差异。在特定目标3中，将在小鼠中干扰LAB基因，以研究LAB在B细胞发育中的作用。我们还将研究实验室在血小板和NK细胞中的功能。表演网站========================================Section End===========================================

EXCEED THE SPACE PROVIDED. Engagement of antigen receptors on T and B cells leads to activation of a series of signaling cascades, including phosphorylation of cellular proteins and activation of the Ras-MAPK pathway and Ca 2+ flux. In T cells, the membrane-associated adaptor molecule, LAT (Linker for activation ofT cells), plays a crucial role in connecting the TCR engagement to Ras-MAPK activation and Ca 2+ flux by recruiting Grb2, Gads, and PLC-y1 to the membrane. However, it is not clear how the BCR engagement is coupled to Ras-MAPK activation and Ca 2¿ flux. A LAT-like molecule has not been found in B cells. Recently, we cloned a novel gene encoding a membrane-associated adaptor protein. We named this gene, LAB (Linker for activation of B cells). Our preliminary data showed that LAB shares many characteristics with LAT. We hypothesize that, in B cells, LAB functions to couple the BCR engagement to downstream Ras-MAPK activation and Ca 2+ flux by recruiting Grb2 to the membrane. This proposal aims to further study LAB function in B cell activation and development. Three specific aims are designed to test this hypothesis. In specific aim 1, LAB gene will be disrupted in the chicken DT40 B cell line. Signaling defects caused by deletion of this gene will be characterized. In specific aim 2, we will examine the functional differences between LAB and LAT using transgenic mice. In specific aim 3, LAB gene will be disrupted in mice to study LAB function in B cell development. We will also study LAB function in platelets and NK cells. PERFORMANCE SITE ========================================Section End===========================================