Signal Transduction in Time and Space

描述(由申请人提供)：本计划项目申请的目标是了解细胞表面受体、蛋白质和脂蛋白激酶、磷酸酶和GTP酶在四维过程中的信号传递，该过程由肌动蛋白细胞骨架、适配蛋白和靶向分子组织和加速。要了解信号是如何在时间和空间中传播的，需要识别将分子定向到确定的细胞内间隔所需的新型分子支架，需要新的实验方法来测量细胞内产生的信号，以及更好地了解信号传播和调节的动力学。信号转导的空间和时间分析是理解正常细胞调控的基础，也是理解异常细胞信号过程的关键，而异常细胞信号过程是癌细胞的中心特征。该计划项目致力于通过营造一个高度互动的环境来促进对细胞信号在时间和空间上的分析，在这种环境中，思想、专业知识和技术资源的交流在时间和空间上自由而有效地发生。在第一个项目中，Parsons和Horwitz专注于了解蛋白酪氨酸激酶和小GTP酶在细胞黏附组装和周转的空间和时间调节中的作用。在第二个项目中，Brautigan和Eto将研究靶向细胞磷酸酶亚单位如何定位于动态重组的位置，如黏附复合体和细胞-细胞连接。这些蛋白质被磷酸化激活，并整合多种信号来控制细胞中的肌动蛋白组织，这是动员驱动细胞迁移和细胞极化所需的张力的关键步骤。该计划得到了显微镜核心的支持，该核心为该计划提供尖端成像能力、图像分析和培训。

DESCRIPTION (provided by applicant): The goal of this Program Project application, entitled "Signal Transduction in Time and Space", is to understand cell signaling by cell surface receptors, protein and lipid kinases, phosphatases and GTPases within the context of a four dimensional process, organized and expedited by the actin cytoskeleton, adapter proteins and targeting molecules. Understanding how signals are propagated in time and space requires the identification of novel molecular scaffolds required for targeting molecules toward defined intracellular compartments, new experimental approaches for measuring signals generated in intracellular compartments, and a better understanding of the dynamics of signal propagation and regulation. The spatial and temporal analysis of signal transduction is fundamental to understanding normal cellular regulation and critical to understanding abnormal cellular signaling processes, central hallmarks of cancer cells. The Program Project endeavors to facilitate the analysis of cellular signaling in time and space by fostering a highly interactive environment, one in which exchanges of ideas, expertise and technical resources occur freely and efficiently in time and space. In the first Project, Parsons and Horwitz focus on understanding the role of protein tyrosine kinases and small GTPases in the spatial and temporal regulation of cell adhesion assembly and turnover. In the second Project, Brautigan and Eto will examine how targeting subunits of cellular phosphatases localize to sites of dynamic reorganization, such as adhesion complexes and cell-cell junctions. These proteins are activated by phosphorylation and integrate multiple signals to control actin organization in cells, a key step in mobilizing the tensional forces needed to drive cell migration and cell polarization. The Program is supported by aMicroscopy Core that provides cutting edge imaging capabilities, image analysis and training to the Program.