Role of membrane defects in the regulation of the activity of protein kinase C.

With mixtures of phosphatidylethanolamine and phosphatidylserine, the activity of protein kinase C is highly dependent on the fatty acid composition of the phosphatidylethanolamine. This contrasts with phosphatidylcholine/phosphatidylserine mixtures which affect the activity of PKC in a manner independent of the fatty acid composition of the phosphatidylcholine. The results are in accord with those phospholipids having the lowest bilayer-hexagonal phase transition temperature being most effective in augmenting the activity of PKC in the presence of its cofactors. Although the activity of this enzyme is markedly sensitive to the presence of hexagonal phase forming lipids, the activity is insensitive to differences between gel and liquid crystalline state membranes. Membrane defects alone also do not explain the observed effects since vesicles with phase boundary defects do not activate PKC. Increased hexagonal phase propensity of the lipid does not alter the partitioning of PKC between aqueous and membrane phases, which remains calcium dependent. The results demonstrate that simply the formation of defects is not sufficient to promote PKC activity, but that changes in membrane bilayer properties related to hexagonal phase propensity are required.