Components of Ras-Mediated Growth Control

Ras家族GTP酶是控制增殖的细胞调节系统的关键组分， 分化和细胞存活。对这些系统的不适当调节直接导致初始化 和人类癌症的发展。这一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 重点是介导致癌Ras诱导的细胞转化的主要效应途径。我们 具体目的是：1）揭示Ral GTP酶支持人类免疫功能的分子基础， 肿瘤细胞增殖和存活; 2）评估两种候选Ras效应物在限制细胞增殖和存活中的作用， 对促有丝分裂信号的反应;和3）定义支架蛋白对产生促有丝分裂信号的贡献。 ERK 1/2 MAP激酶级联信号保真度。

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..