Abstract

We wish to continue our studies into the mechanism of action of cellular and viral oncogenes in proliferation and differentiation. By combining molecular biological techniques with cell biological ones, we have been able to establish unique assays for the analysis of the function of the cellular ras protooncogene and oncogene proteins in proliferation and differentiation, and for the analysis of the biological and biochemical activity of the src protooncogene and oncogene proteins. We will continue to evaluate the biological and biochemical changes that occur in living cells microinjected with the purified ras proteins or with neutralizing antibodies directed against these proteins. We will examine the biochemical role of the ras proteins in the regulation of phospholipid turnover and intracellular pH, as suggested by our microinjection studies. Likewise, we will continue our newly begun studies of the function of the src proteins in proliferation and differentiation. For these we have utilized monoclonal antibodies to c- and v-src and have begun to use baculovirus expression vectors for the production of the src proteins in insect cells. Through this work, we hope to continue contributing to the understanding of the mechanism of cellular transformation by oncogenes, and in parallel to the understanding of the normal biological roles of the cellular protooncogene proteins in proliferation and differentiation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039811-08
Application #
3179212
Study Section
Molecular Biology Study Section (MBY)
Project Start
1988-04-05
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1994-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

LaMorte, V J; Kennedy, E D; Collins, L R et al. (1993) A requirement for Ras protein function in thrombin-stimulated mitogenesis in astrocytoma cells. J Biol Chem 268:19411-5
Sosnowski, R G; Feldman, S; Feramisco, J R (1993) Interference with endogenous ras function inhibits cellular responses to wounding. J Cell Biol 121:113-9
Walton, P A; Gould, S J; Rachubinski, R A et al. (1992) Transport of microinjected alcohol oxidase from Pichia pastoris into vesicles in mammalian cells: involvement of the peroxisomal targeting signal. J Cell Biol 118:499-508
Lin, A; Frost, J; Deng, T et al. (1992) Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. Cell 70:777-89
Walton, P A; Gould, S J; Feramisco, J R et al. (1992) Transport of microinjected proteins into peroxisomes of mammalian cells: inability of Zellweger cell lines to import proteins with the SKL tripeptide peroxisomal targeting signal. Mol Cell Biol 12:531-41
Fantozzi, D A; Taylor, S S; Howard, P W et al. (1992) Effect of the thermostable protein kinase inhibitor on intracellular localization of the catalytic subunit of cAMP-dependent protein kinase. J Biol Chem 267:16824-8
Lamb, N J; Fernandez, A; Feramisco, J R et al. (1989) Modulation of vimentin containing intermediate filament distribution and phosphorylation in living fibroblasts by the cAMP-dependent protein kinase. J Cell Biol 108:2409-22
Lamb, N J; Fernandez, A; Conti, M A et al. (1988) Regulation of actin microfilament integrity in living nonmuscle cells by the cAMP-dependent protein kinase and the myosin light chain kinase. J Cell Biol 106:1955-71
Bar-Sagi, D; Gomperts, B D (1988) Stimulation of exocytotic degranulation by microinjection of the ras oncogene protein into rat mast cells. Oncogene 3:463-9
Bar-Sagi, D; Suhan, J P; McCormick, F et al. (1988) Localization of phospholipase A2 in normal and ras-transformed cells. J Cell Biol 106:1649-58

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