This proposal focuses on the relation between the cell biology (localization,targeting) of trimeric G proteins and their ability to transduce signals. Experiments will: 1) Elucidate key steps in the localization mechanisms that target G protein alpha and beta-gamma subunits to the plasma membrane and determine where and when they become capable of transducing signals from the receptor to the effector. 2) Assess the role of G-alpha palmitoylation, a lipid modification that may serve to retain these subunits at the plasma membranes and determine how these mechanisms modulate G protein mediated signals inintiated by receptor agonists. 3) Identify cellular proteins that associate with G-beta-gamma subunits and mediate cellular proliferation and (potentially) neoplastic transformation via activation of the MAPK/ERK pathway. 4) Define interactions of the G-alpha with three proteins - actin, caveolin and members of the G-alpha-interacting protein (GAIP) family-that may inhibit G protein signaling by interacting with and sequestering G-alpha subunit.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054427-19
Application #
2871759
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Spalholz, Barbara A
Project Start
1991-08-01
Project End
2002-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
19
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Wedegaertner, P B; Bourne, H R; von Zastrow, M (1996) Activation-induced subcellular redistribution of Gs alpha. Mol Biol Cell 7:1225-33

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