Cell adhesion plays a fundamental role in the proliferation and motility of normal cells. Transmembrane integrin receptor binding to extracellular matrix proteins (ECM) such as fibronectin (FN) mediates cell adhesion, stimulates cell spreading, and also initiates intracellular signal transduction events important for anchorage-dependent cell growth. One such signal, the increased tyrosine phosphorylation of cellular proteins, is a common response to integrin receptor binding to ECM proteins. However, since integrin receptors lack intrinsic protein-tyrosine kinase (PTK) activity, these events must be mediated by associated proteins. The cytoplasmic non-receptor focal adhesion (FAK) protein-tyrosine associates with integrins and is activated by FN stimulation of cells. Transient-binding of Src-family PTKs and the Grb2 adaptor protein to FAK has established that an integrin-activated FAK complex can generate signals to downstream targets such as extracellular signal-regulated ERK2/MAP kinase. The mouse FAK gene knockout is lethal and FAK-fibroblasts exhibit a round cell morphology, form an enhanced number of substratum contacts in cell culture, and exhibit reduced rates of integrin-stimulated migration. The general aims of this study are to biochemically characterize the FN-stimulated signaling network present in the FAK-cells. In addition, the retroviral-mediated expression of FAK and the related PTK Pyk2 in the FAK-cells, will attempt to determine the functional similarities or differences between these two PTKs, and evaluate the molecular interactions needed to reverse some of the FAK-deficient cell phenotypes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29CA075240-01
Application #
2382823
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1997-07-01
Project End
2002-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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