Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039438-14
Application #
2654001
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
1998-02-01
Budget End
1999-01-31
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Virginia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

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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