Components of Ras-Mediated Growth Control

描述（由申请人提供）：Ras家族gtpase是控制细胞增殖、分化和细胞存活的细胞调节系统的关键组成部分。这些系统的不当调控直接导致人类癌症的发生和发展。这一建议旨在增加我们对Ras家族GTPases参与的细胞调控网络的组成、组织和功能的理解。我们的重点是主要的效应途径，介导致癌ras诱导的细胞转化。我们的具体目标是：1)揭示Ral GTPases支持人类肿瘤细胞增殖和存活的分子基础；2)评估两种候选Ras效应物在限制细胞对有丝分裂信号的反应中的作用；3)确定支架蛋白对ERK1/2 MAP激酶级联信号保真度产生的贡献。

DESCRIPTION (provided by applicant): 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.