UNDERSTANDING THE ROLES OF SMALL GTPASES IN CELL GROWTH REGULATION

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。 我们的研究目标是将结构方法与细胞生物学和遗传学研究相结合，以便更好地了解有助于细胞生长和分化的基本过程。这项结构性工作需要两条线的实验工作，而且越来越复杂。第一个涉及理解GTP结合蛋白(GTP酶)激活(GTP结合)和失活(GTP水解)的构象变化。我们一直使用CDC42和相关的小GTP酶(如RhoC)作为这些研究的模型，它们在协调细胞周期进程和增殖与细胞形状变化和细胞迁移方面发挥关键作用。第二条主要研究方向是确定多蛋白复合体的作用机制和结构基础，这些复合体直接激活CDC42并调节其细胞反应。

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. The goal of our research has been to combine structural approaches with cell biology and genetic studies in order to better understand fundamental processes that contribute to the growth and differentiation of cells. The structural work entails two lines of experimental efforts of increasing complexity. The first involves understanding the conformational changes underlying the activation (GTP-binding) and deactivation (GTP hydrolysis) of GTP-binding proteins (GTPases). We have been using Cdc42 and related small GTPases (e.g. RhoC), which play critical roles in coordinating cell cycle progression and proliferation with cell shape changes and cell migration, as models for these studies. A second major line of study is directed toward determining the mechanistic and structural basis for the actions of multi-protein complexes that direct the activation of Cdc42 and mediates its cellular responses.