SIGNALING AND CYTOSKELETAL ORGANIZATION IN BLOOD CELLS

描述（申请人提供）： 拟议的计划项目是基于我们的中心假设，即新的信号 通路参与血细胞活化后的细胞骨架重组。朝向 为此，我们通过同源重组靶向某些相关基因：Wiskott-Aldrich 综合征蛋白，N-WASP，WASP相互作用蛋白，Vav 1和Vav 3，Cdc 42 和Rac。我们现在计划利用这些“敲除”：从细胞中阐明 细胞骨架重组的表面受体。该项目包括四个项目， 三个核心项目1旨在了解WASP的重叠和非重叠作用 和N-WASP通过鉴定它们的功能结构域以及同源蛋白质的功能结构域， WAVE-2的表达，并确定GTP酶Cdc 42和Rac 1在淋巴细胞中的作用， 发展和功能。项目二是研究控制器在控制过程中的作用 WASP和N-WASP激活肌动蛋白聚合。Brugge博士研究了Vav 1、2和3对单核细胞和中性粒细胞趋化性的影响。Rao博士将研究淋巴细胞中钙流与无反应性细胞骨架通路功能的关系，以及T细胞中钙流与细胞骨架通路功能的关系。 细胞激活核心A将管理该计划。

DESCRIPTION (provided by the Applicant): The proposed program project is based on our central hypothesis that novel signaling pathways are involved in cytoskeletal re-organization upon activation of blood cells. Toward this end we targeted certain relevant genes by homologous recombination: Wiskott-Aldrich syndrome protein (WASP); N-WASP, WASP interactive protein (WIP), Vav 1 and Vav 3, Cdc42 and Rac. We now plan to exploit these "knock-out": to elucidate the pathway(s) from cell surface receptors to cytoskeletal re-organization. The proposal consists of four projects and three cores. Project 1 seeks to understand the overlapping and non-overlapping roles of WASP and N-WASP by identifying their functional domains as well as those of the homologous protein WAVE-2 and to determine the roles of the GTPases, Cdc42 and Rac1, in lymphocyte development and function. Project 2 is devoted to a study of the function of WIP in the control of WASP and N-WASP activation for actin polymerization. Dr. Brugge studies the effect of Vav 1, 2 and 3 on chemotaxis of monocytes and neutrophils. Dr. Rao will study the relationship of calcium flux in lymphocytes to the function of the cytoskeletal pathways in anergy as well as T cell activation. Core A will administer the program.