Components of Ras-Mediated Growth Control

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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.