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Abstract
Grant Number: 2R37CA017542-28 Project Title: Genetics of RNA Tumor Viruses
PI Information: Name Title MARTIN, G STEVEN. gsm@berkeley.edu PROFESSOR AND HEAD Abstract: DESCRIPTION (provided by applicant): The non-receptor tyrosine kinase Src is activated in many human breast and colon cancers. The long term goals of this project are to characterize the signaling pathways involved in transformation by mutationally activated Src, using retroviral Src, v-Src, as a model, and to compare these signaling pathways with those that are physiologically regulated by endogenous cellular Src, c-Src. The first specific aim concerns the mechanism by which Src remodels the cytoskeleton to induce cell motility and invasion, and in particular the role of Rho family GTPases in this process. The mechanism by which RhoA is activated and the effects of blocking Rho signaling will be determined. The mechanism by which Src affects Rho effector pathways will also be examined. The second specific aim concerns the effects of Src on cell proliferation and programmed cell death (apoptosis), and in particular the role of the transcription factor E2F1 in these processes. E2F1 undergoes tyrosine phosphorylation in v-Src-transformed cells. The kinase responsible for this phosphorylation will be identified and the effect of tyrosine phosphorylation on E2F1 function will be determined. The third specific aim concerns the effect of Src on gene expression and the differences between transient signaling by c-Src and constitutive signaling by v-Src. The effects of v-Src and c-Src will be compared by microarray analysis. Transcriptional targets of Myc that are required for Src transformation will be identified. The expression of certain Myc targets is rendered Myc-independent in v-Src-transformed cells, and the mechanism by which this occurs will be determined.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
RNA virus, biological signal transduction, neoplastic transformation, protein tyrosine kinase, transforming virus, virus genetics
Rous sarcoma virus, apoptosis, cell proliferation, cytoskeleton, enzyme activity, guanine nucleotide binding protein, phosphopeptide, phosphorylation, transcription factor
cell line, chick embryo, fibroblast, laboratory rabbit, mass spectrometry, microarray technology, western blotting
Institution: UNIVERSITY OF CALIFORNIA BERKELEY 2150 Shattuck Avenue, Room 313 BERKELEY, CA 947045940 Fiscal Year: 2003 Department: MOLECULAR AND CELL BIOLOGY (MCB) Project Start: 01-DEC-1978 Project End: 31-DEC-2007 ICD: NATIONAL CANCER INSTITUTE IRG: VR