Components of Ras-Mediated Growth Control

RAS家族GTP酶是控制细胞增殖的细胞调控系统的重要组成部分， 分化和细胞存活。对这些系统的不适当监管直接导致了启动 以及人类癌症的进展。这项建议旨在增加我们对 RAS家族GTP酶参与的细胞调控网络的组成、组织和功能。我们的 焦点集中在介导致癌RAS诱导的细胞转化的主要效应通路上。我们的 其具体目的是：1)揭示Ral GTP酶对人类免疫缺陷的分子基础 肿瘤细胞的增殖和存活；2)评估两个候选RAS效应因子在限制细胞 对有丝分裂信号的反应；以及3)确定支架蛋白对产生 ERK1/2信号通路的信号保真度。

Ras family GTPases are critical components of cell regulatory systems that control proliferation, differentiation, and cell survival. Inappropriate regulation of these systems directly contributes to initiation and progression of human cancer. This proposal is directed at increasing our understanding of the composition, organization, and function of cell regulatory networks engaged by Ras family GTPases. Our focus is on the dominant effector pathways that mediate oncogenic Ras-induced cell transformation. Our specific aims are 1) revealing the molecular basis of the contribution of Ral GTPases to support of human tumor cell proliferation and survival; 2) assessing the role of two candidate Ras effectors in limiting cellular responses to mitogenic signals; and 3) defining the contribution of scaffolding proteins to the generation of signal fidelity on the ERK1/2 MAP kinase cascade..