Previously, ethanol and the protein kinase C (PKC) activators phorbol 12-myristate 13-acetate (PMA) and bombesin were shown to synergistically stimulate phospholipase C (PLC)-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) in NIH 3T3 fibroblasts. Here we used fibroblasts overexpressing PKC-ϵ 15-fold to examine the possible role of this enzyme in the regulation of PtdEtn hydrolysis by ethanol. Overexpressed PKC-ϵ (i) greatly enhanced the stimulatory effects of ethanol (37.5–150 mM) on PLC-mediated PtdEtn hydrolysis, and (ii) eliminated the need for the co-presence of a PKC activator for maximal (3,3-fold) stimulation of PLC by 150 mM ethanol. Results suggest that PKC-ϵ is a potential positive regulator of the PtdEtn-hydrolyzing PLC activity, and that the functional interaction between PKC-ϵ and PLC is facilitated by ethanol.
