Lipid-dependent activation of protein kinase C-alpha by normal alcohols

Significant stimulation of protein kinase C-alpha (PKC alpha) by n-alcohols was observed in characterized lipid systems composed of phosphatidylcholin e/phosphatidylserine/dioleoylglycerol (PC/PS/DO), The logarithm of the alco hol concentrations to achieve half-maximal PKC stimulation (ED50) and of th e maximal PKC stimulation by alcohols were both linear functions of alcohol chain length, consistent with the Meyer-Overton effect. Binding of phorbol esters to PKC was not significantly affected by octanol, Octanol increased , up to 4-fold, the affinity of PKC binding to the lipid bilayers in both t he absence and presence of DO. However, octanol increased PKC activity much more significantly than it enhanced binding of the enzyme to the lipid bil ayers, suggesting that the stimulation of PKC is not merely a reflection of the increase in PKC bilayer binding affinity. P-31 NMR experiments did not reveal formation of non-lamellar phases with octanol, Differential scannin g calorimetry suggested that alcohols, like diacylglycerol, induce formatio n of compositionally distinct domains and the maximal enzyme activity with alcohol resided roughly in the putative domain-coexistence region. These re sults suggest that alcohols are mimicking diacylglycerol in activating PKC, not by binding to the high affinity phorbol ester binding site, but by alt ering lipid structure and by enhancing PCK-bilayer binding.