Signal Transduction in Time and Space

描述（由申请人提供）：本项目申请的目标是“时间和空间中的信号转导”，旨在了解细胞表面受体、蛋白质和脂质激酶、磷酸酶和gtp酶在四维过程中的信号传导，由肌动蛋白细胞骨架、适配器蛋白和靶向分子组织和加速。理解信号是如何在时间和空间上传播的，需要识别新的分子支架，将分子靶向到定义的细胞内区室，新的实验方法来测量细胞内区室产生的信号，以及更好地理解信号传播和调节的动力学。信号转导的时空分析是理解正常细胞调控的基础，也是理解异常细胞信号传导过程（癌细胞的中心特征）的关键。本项目通过营造一个高度互动的环境，使思想、专业知识和技术资源在时间和空间上自由有效地交流，努力促进对细胞信号的时间和空间分析。在第一个项目中，Parsons和Horwitz专注于了解蛋白酪氨酸激酶和小gtpase在细胞粘附组装和周转的时空调节中的作用。在第二个项目中，Brautigan和Eto将研究细胞磷酸酶的靶向亚基如何定位于动态重组位点，如粘附复合物和细胞-细胞连接。这些蛋白被磷酸化激活，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。该计划由aMicroscopy Core提供支持，该公司为该计划提供尖端的成像能力、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.