It is the goal of this study to understand the regulation and expression of protein kinase C, a major receptor for tumor promoters which has been implicated in the process of hormone-mediated cellular mitogenesis as well as tumor promotion. Having demonstrated that the epidermal growth factor receptor is a biological target of protein kinase C action, our initial aim is to use this system following treatment with tumor promoters to determine the number and nature of the different activation states of C kinase. Once the level of active enzyme required to induce a biological response is determined, we will explore the role of C kinase in the action of different growth enhancers on nontransformed cells. The differences in protein kinase C activity in transformed relative to nontransformed cells will be analyzed, as well as the causes of C kinase inactivation. Finally, we plan to prepare antibody directed against protein kinase C as an aid in achieving these goals. An understanding of the factors which regulate the activation of protein kinase C should provide valuable information regarding the mechanisms of mitogenic stimulation, hormonal regulation, and the onset of tumor promotion.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA040407-01
Application #
3180283
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
Friedman, B; Fujiki, H; Rosner, M R (1990) Regulation of the epidermal growth factor receptor by growth-modulating agents: effects of staurosporine, a protein kinase inhibitor. Cancer Res 50:533-8
Hicks, K; Friedman, B; Rosner, M R (1989) Basic fibroblast-like growth factor is present in the conditioned medium of simian sarcoma virus transformed NRK cells. Biochem Biophys Res Commun 164:1323-30
Hicks, K; Friedman, B; Rosner, M R (1989) Basic and acidic fibroblast growth factors modulate the epidermal growth factor receptor by a protein kinase C-independent pathway. Biochem Biophys Res Commun 164:796-803
Wattenberg, E V; McNeil, P L; Fujiki, H et al. (1989) Palytoxin down-modulates the epidermal growth factor receptor through a sodium-dependent pathway. J Biol Chem 264:213-9
Friedman, B A; van Amsterdam, J; Fujiki, H et al. (1989) Phosphorylation at threonine-654 is not required for negative regulation of the epidermal growth factor receptor by non-phorbol tumor promoters. Proc Natl Acad Sci U S A 86:812-6
Takishima, K; Friedman, B; Fujiki, H et al. (1988) Thapsigargin, a novel promoter, phosphorylates the epidermal growth factor receptor at threonine 669. Biochem Biophys Res Commun 157:740-6
Friedman, B A; Rosner, M R (1987) Growth factors modify the epidermal growth factor receptor through multiple pathways. J Cell Biochem 34:1-11
McCaffrey, P G; Rosner, M R (1987) Growth state-dependent regulation of protein kinase C in normal and transformed murine cells. Cancer Res 47:1081-6
McCaffrey, P G; Rosner, M R; Kikkawa, U et al. (1987) Characterization of protein kinase C from normal and transformed cultured murine fibroblasts. Biochem Biophys Res Commun 146:140-6
Wattenberg, E V; Fujiki, H; Rosner, M R (1987) Heterologous regulation of the epidermal growth factor receptor by palytoxin, a non-12-O-tetradecanoylphorbol-13-acetate-type tumor promoter. Cancer Res 47:4618-22

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