9558439 Newton Protein kinase C transduces signals that promote phospholipid hydrolysis. Binding of a wide variety of signals to cell surface receptors results in phospholipase C-catalyzed hydrolysis of phosphatidylinositol bisphosphate, producing the water soluble head-group, inositol trisphosphate, and the lipid backbone, diacylglycerol. Both molecules are critical second messengers in the protein kinase C signalling pathway. Inositol trisphosphate mobilizes intracellular Ca2+ thus causing protein kinase C, which is present in the cytosol under resting conditions, to bind to the plasma membrane. Diacylglycerol activates the kinase; activity also requires the amino phospholipid, phosphatidylserine. The long-term objective of the proposed research is to understand the mechanism of action of protein kinase C. Specifically, the role of diayclglycerol in regulating the enzyme will be addressed. The hypotheses that 1) diacylglycerol targets protein kinase C to the plasma membrane, and 2) diacylglycerol is an allosteric activator of the kinase will be tested. %%% The effect of diacylglycaerol on the protein kinase C membrane interaction, and on the conformation of protein kinase C, will be addressed with the aim of understanding how this second messenger regulates the structure and function of protein kinase C, and in turn, signal transduction. ***
