UNDERSTANDING THE ROLES OF SMALL GTPASES IN CELL GROWTH REGULATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 我们研究的目标是将联合收割机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。 结构工作需要两条线的实验努力日益复杂。 第一个涉及到理解GTP结合蛋白（GTP酶）的激活（GTP结合）和失活（GTP水解）的构象变化。 我们一直在使用Cdc 42和相关的小GTP酶（如RhoC），这在协调细胞周期进程和增殖与细胞形状变化和细胞迁移，作为这些研究的模型中发挥关键作用。 第二个主要的研究方向是确定多蛋白复合物的作用机制和结构基础，这些复合物直接激活Cdc 42并介导其细胞反应。

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.