Abstract

Genetic and biochemical experiments have shown that the product of the Rous sarcoma virus src gene is required for the initiation and maintenance of cellular transformation. As a part of our long-term goal of understanding how the src gene product, pp60src, mediates the molecular events involved in cellular transformation, we have isolated and partially characterized monoclonal antibodies directed against pp60src. The experiments outlined in this proposal employ monoclonal antibodies to unique determinants within pp60src as immunochemical probes to define and characterize the structural and functional domains of the molecule and attempt to elucidate the role of individual functional domains in mediating cellular transformation. We further propose to utilize monoclonal antibodies to pp60src as immunochemical probes to compare the structure and function of other retrovirus tyrosine protein kinase as well as normal cell tyrosine protein kinases. These studies will permit us to define the structural and functional domains of pp60src and allow us to relate this information to other proteins which may be members of a family of related tyrosine protein kinases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029243-10
Application #
3168595
Study Section
Experimental Virology Study Section (EVR)
Project Start
1981-01-01
Project End
1992-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

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

  Publications

Parsons, J Thomas; Slack-Davis, Jill; Tilghman, Robert et al. (2008) Focal adhesion kinase: targeting adhesion signaling pathways for therapeutic intervention. Clin Cancer Res 14:627-32
Iwanicki, Marcin P; Vomastek, Tomas; Tilghman, Robert W et al. (2008) FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts. J Cell Sci 121:895-905
Owen, Katherine A; Pixley, Fiona J; Thomas, Keena S et al. (2007) Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. J Cell Biol 179:1275-87
Vomastek, Tomas; Iwanicki, Marcin P; Schaeffer, Hans-Joerg et al. (2007) RACK1 targets the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to link integrin engagement with focal adhesion disassembly and cell motility. Mol Cell Biol 27:8296-305
Martin, Karen H; Jeffery, Erin D; Grigera, Pablo R et al. (2006) Cortactin phosphorylation sites mapped by mass spectrometry. J Cell Sci 119:2851-3
Liu, Yunhao; Yerushalmi, Gil M; Grigera, Pablo R et al. (2005) Mislocalization or reduced expression of Arf GTPase-activating protein ASAP1 inhibits cell spreading and migration by influencing Arf1 GTPase cycling. J Biol Chem 280:8884-92
Slack-Davis, Jill K; Eblen, Scott T; Zecevic, Maja et al. (2003) PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation. J Cell Biol 162:281-91
Kinley, Andrew W; Weed, Scott A; Weaver, Alissa M et al. (2003) Cortactin interacts with WIP in regulating Arp2/3 activation and membrane protrusion. Curr Biol 13:384-93
Head, Julie A; Jiang, Dongyan; Li, Min et al. (2003) Cortactin tyrosine phosphorylation requires Rac1 activity and association with the cortical actin cytoskeleton. Mol Biol Cell 14:3216-29
Parsons, J Thomas (2003) Focal adhesion kinase: the first ten years. J Cell Sci 116:1409-16

Showing the most recent 10 out of 89 publications