The long-term goal of this proposal is to understand the role of RhoA, a small GTPase that induces actin stress fibers, in v-Src transformation. In cells, v-Src, an activated form of the c-Src tyrosine kinase, is thought to promote transformation by continually stimulating normally transient signaling pathways. In fact, certain human cancers have elevated c-Src activity, and tumor progression correlates with the Src activity level. Several studies suggest that v-Src decreases RhoA[GTP] levels, and that this causes actin stress fiber loss in transformed cells. ? However, evidence from our laboratory indicates v-Src activity enhances RhoA[GTP] levels. RhoA is also required for the proliferation of non-transformed cells, likely by regulating the timing of expression of key cell cycle regulators and sustaining MAPK activity during cell cycle progression. These observations have led to the following general hypothesis: v-Src induced mitogenic transformation requires RhoA signaling, but v-Src induced actin stress fiber disassembly and cell motility, circumvent RhoA signaling.
Three Specific Aims will test this hypothesis: 1) Investigate the requirement for RhoA signaling in v-Src-mediated mitogenic transformation. 2) Determine the mechanism by which v-Src induces cofilin activation. 3) Evaluate the significance of cofilin activation on cell migration and invasion in cells with elevated Src kinase activity. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM068319-01
Application #
6649098
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Flicker, Paula F
Project Start
2003-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
1
Fiscal Year
2003
Total Cost
$41,608
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704