Ras-mediated signal transduction pathways are highly conserved among metazoan and play key roles in controlling cell proliferation and differentiation. Mutant forms of two members of the pathway, ras and raf, are among the most commonly seen oncogenes involved in many types of cancers. Through a genetic suppresser-of-ras screen in the nematode C. elegans, several conserved regulators of Ras-Raf activation were discovered. One such gene, sur-8, encodes a conserved Leucine-Rich Repeat protein that binds directly to Ras and plays an important role in Ras regulation. I propose to study the regulation of signaling activity transmitted by Ras by focusing on two genes which have been shown to act positively to regulate Ras-Raf activation. C. elegans genetics, in vitro biochemistry, and possibly mammalian cell culture systems will be used. I will study the role of the sur-8 gene in mediating ras signal transduction by examining the nature of SUR-8 interactions with both Ras and Raf. I will also use molecular methods including two-hybrid techniques to identify other protein(s) that I may interact and function with SUR-8 to facilitate Ras-pathway activation. I will also genetically and molecularly characterize another suppresser gene, sur-7, which appears to also function as a positive regulator in the pathway. Work in the past several years demonstrated that vulval induction in C. elegans provides a specific assay system to identify new genes and elucidate their functions in signal transduction.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020029-02
Application #
6342753
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Tompkins, Laurie
Project Start
2000-01-01
Project End
Budget Start
2001-01-01
Budget End
2001-09-15
Support Year
2
Fiscal Year
2001
Total Cost
$33,730
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309