Abstract

The cellular src gene product displays a unique pattern of expression in neuronal cells that differs qualitatively and quantitatively from that found in other cell (designated pp60 c- src(+)) which contains a 6-amino acid insert within the amino- terminal region of the protein. This insert appears to be a consequence of a unique pattern of c-src mRNA splicing in neurons since c-src cDNA clones isolated from chicken and mouse brain cDNA libraries contain an 18-nucleotide insert located between the exons 3 and 4. The finding that neurons specifically express high levels of an altered form of pp60 c-src, and the evidence that tyrosine kinases are involved in pp60 c-src may play a role in regulating neuronal cell function. This proposal describes plans to further characterize the functional activity of this unique form of pp60 c-src and its localization in neural tissues. We also will examine how expression to isolate and characterize cellular proteins that might interact with pp60 c-src(4) to regulate its functional activity. These experiments should provide clues to the function of pp60 c-src which serves as a model protein for the src-family of proto-oncogene products that are associated exclusively with the cytoplasmic face of he plasma membrane, and thus cannot function directly as receptors for peptide hormones.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA047572-03
Application #
3191285
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-04-01
Project End
1993-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Clark, E A; King, W G; Brugge, J S et al. (1998) Integrin-mediated signals regulated by members of the rho family of GTPases. J Cell Biol 142:573-86
King, W G; Mattaliano, M D; Chan, T O et al. (1997) Phosphatidylinositol 3-kinase is required for integrin-stimulated AKT and Raf-1/mitogen-activated protein kinase pathway activation. Mol Cell Biol 17:4406-18
Gao, J; Zoller, K E; Ginsberg, M H et al. (1997) Regulation of the pp72syk protein tyrosine kinase by platelet integrin alpha IIb beta 3. EMBO J 16:6414-25
Rusanescu, G; Qi, H; Thomas, S M et al. (1995) Calcium influx induces neurite growth through a Src-Ras signaling cassette. Neuron 15:1415-25
Clark, E A; Shattil, S J; Ginsberg, M H et al. (1994) Regulation of the protein tyrosine kinase pp72syk by platelet agonists and the integrin alpha IIb beta 3. J Biol Chem 269:28859-64
Clark, E A; Shattil, S J; Brugge, J S (1994) Regulation of protein tyrosine kinases in platelets. Trends Biochem Sci 19:464-9
Clark, E A; Brugge, J S (1993) Redistribution of activated pp60c-src to integrin-dependent cytoskeletal complexes in thrombin-stimulated platelets. Mol Cell Biol 13:1863-71
Fox, J E; Lipfert, L; Clark, E A et al. (1993) On the role of the platelet membrane skeleton in mediating signal transduction. Association of GP IIb-IIIa, pp60c-src, pp62c-yes, and the p21ras GTPase-activating protein with the membrane skeleton. J Biol Chem 268:25973-84
Haimovich, B; Lipfert, L; Brugge, J S et al. (1993) Tyrosine phosphorylation and cytoskeletal reorganization in platelets are triggered by interaction of integrin receptors with their immobilized ligands. J Biol Chem 268:15868-77
Schmidt, J W; Brugge, J S; Nelson, W J (1992) pp60src tyrosine kinase modulates P19 embryonal carcinoma cell fate by inhibiting neuronal but not epithelial differentiation. J Cell Biol 116:1019-33

Showing the most recent 10 out of 19 publications