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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.
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