Amplification of Diacylglycerol Activation of
Protein Kinase C by Cholesterol
Don Leigh Armstrong 1 and Raphael Zidovetzki 1*
1 University of California, Riverside
* To whom correspondence should be addressed. E-mail: zidovet{at}mail.ucr.edu.
Submitted on September 6, 2007
Revised on October 8, 2007
Accepted on 30 January 2008
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Abstract |
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The combined effects of cholesterol, a major cell membrane component, and the lipid second messenger diacylglycerol on the activity of protein kinase C (PK-C) and the structure of phosphatidylcholine/phosphatidylserine bilayers were investigated using specific PK-C assays and 2H NMR. Whereas the classical activation of PK-C was observed as an effect of diacylglycerol, in the absence of this second messenger, cholesterol did not affect PK-C activity. A novel effect of amplified PK-C activation was observed in the presence of both cholesterol and diacylglycerol concentrations within the physiological range of each of these components. 2H NMR results suggest that this phenomenon is due to cholesterol- and diacylglycerol-induced increased propensity of the lipids to adopt non-bilayer phases, effectively destabilizing the bilayer structure. The magnitude of the effect was a function of cholesterol concentration, implying that laterally separated cell membrane domains with distinct cholesterol concentrations have the capacity to differ in their sensitivity to extracellular stimuli.
Key Words:
2H NMR, lipid bilayer structure, membrane domains, signal transduction
