The major focus of the project described in this application is on the GTPase activating protein p190RhoGAP. p190 is known to bind to p120RasGAP and is a substrate for the c-Src tyrosine kinase, findings which led to the suggestion that p190 may link the Ras pathway to Rho-mediated cytoskeletal changes. In this application, the PI proposes to continue functional studies on p190, to identify proteins that interact with p190 using a variety of techniques, and to characterize the function of these proteins in vivo.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039438-15
Application #
2871693
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Cole, John S
Project Start
1985-04-01
Project End
2002-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Virginia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Manukyan, Arkadi; Ludwig, Kirsten; Sanchez-Manchinelly, Sergio et al. (2015) A complex of p190RhoGAP-A and anillin modulates RhoA-GTP and the cytokinetic furrow in human cells. J Cell Sci 128:50-60
Manchinelly, Sergio A Sánchez; Miller, Joyce Agati; Su, Ling et al. (2010) Mitotic down-regulation of p190RhoGAP is required for the successful completion of cytokinesis. J Biol Chem 285:26923-32
Su, Ling; Pertz, Olivier; Mikawa, Masahito et al. (2009) p190RhoGAP negatively regulates Rho activity at the cleavage furrow of mitotic cells. Exp Cell Res 315:1347-59
Mikawa, Masahito; Su, Ling; Parsons, Sarah J (2008) Opposing roles of p190RhoGAP and Ect2 RhoGEF in regulating cytokinesis. Cell Cycle 7:2003-12
Su, Ling; Agati, Joyce M; Parsons, Sarah J (2003) p190RhoGAP is cell cycle regulated and affects cytokinesis. J Cell Biol 163:571-82
Kloth, Michael T; Laughlin, Kristen K; Biscardi, Jacqueline S et al. (2003) STAT5b, a Mediator of Synergism between c-Src and the Epidermal Growth Factor Receptor. J Biol Chem 278:1671-9
Haskell, M D; Slack, J K; Parsons, J T et al. (2001) c-Src tyrosine phosphorylation of epidermal growth factor receptor, P190 RhoGAP, and focal adhesion kinase regulates diverse cellular processes. Chem Rev 101:2425-40
Haskell, M D; Nickles, A L; Agati, J M et al. (2001) Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for EGF-induced actin disassembly in C3H10T1/2 fibroblasts. J Cell Sci 114:1699-708
Biscardi, J S; Ishizawar, R C; Silva, C M et al. (2000) Tyrosine kinase signalling in breast cancer: epidermal growth factor receptor and c-Src interactions in breast cancer. Breast Cancer Res 2:203-10
Roof, R W; Dukes, B D; Chang, J H et al. (2000) Phosphorylation of the p190 RhoGAP N-terminal domain by c-Src results in a loss of GTP binding activity. FEBS Lett 472:117-21

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