Protein kinase C is activated by tumor promotors and there is strong evidence that it actually mediates tumor promotion. Activated protein kinase C phosphorylates the epidermal growth factor receptor, guanylate cyclase and several other potentially regulatory proteins; the physiological significance of this phosphorylation is under study in a number of laboratories. In phase I, we propose to determine the substrate specificity of protein kinase C for defined synthetic peptides, produce antibodies directed against the optimized peptide substrate, synthesize inhibitors of protein kinase C, develop specific assays for protein kinase C catalyzed phosphorylation and develop fluorescent peptides to visualize protein kinase C in cells. The results of phase I research will point the way toward the design of a serum based diagnostic assay for protein kinase C and will protentially lead to the development of potent inhibitors of protein kinase C. The impact of such inhibitors of tumor promotion on human cancer prevention could be highly beneficial. Such inhibitors of protein kinase C might also have application in the areas of cancer treatment, immunomodulation and cancer research. The economic impact of diagnostic and therapeutic protein kinase C reagents for Oncogene Science, Inc. will be major, and as an interim step we plan to add peptide substrates specific for protein kinase C to the Company's research reagent product line.
