Molecular strategies for the dominant inhibition of protein kinase C

• Published in: Endocrine research Vol. 22; no. 4; p. 621
• Main Authors: Parissenti, A M, Kirwan, A F, Kim, S A, Colantonio, C M, Schimmer, B P
• Format: Journal Article
• Language: English
• Published: England 01.11.1996
• Subjects: Adrenal Cortex Neoplasms; Animals; Binding, Competitive; Enzyme Inhibitors - pharmacology; Gene Transfer Techniques; Glutathione Transferase - genetics; Humans; Mice; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - chemistry; Protein Kinase C - genetics; Recombinant Fusion Proteins - pharmacology; Regulatory Sequences, Nucleic Acid; Saccharomyces cerevisiae - genetics; Tumor Cells, Cultured
• ISSN: 0743-5800
• DOI: 10.1080/07435809609043756

The regulatory (R) domain of PKC alpha fused to glutathione-S-transferase (GST-R alpha) competitively inhibited PKC activity associated with extracts of Y1 mouse adrenocortical tumor cells and the activities of several specific PKC isozymes. GST-R alpha did not inhibit the activities of cAMP-dependent protein kinase, cGMP-dependent protein kinase or calmodulin-dependent myosin light chain kinase. GST-R alpha inhibited PKC activities 20 times more potently than did a synthetic peptide corresponding to the pseudosubstrate sequence of PKC alpha. In intact yeast cells, the R domain prevented PKC beta-1-induced inhibition of growth and cytokinesis. These results indicate that the R domain of PKC alpha acts as a specific, dominant inhibitor of PKC activity, and suggest that the PKC alpha R domain may provide a useful genetic tool to assess the roles of PKC in various signal transduction processes.