12-O-tetradecanoylphorbol-13-acetate activates phosphatidylethanol and phosphatidylglycerol synthesis by phospholipase D in cell lysates.

A cell-free system for the synthesis of phosphatidylalcohols was developed in sonicates of HL-60 cells. With [32P]phosphatidylcholine as the exogenous substrate, both phosphatidylethanol and phosphatidylglycerol were formed through a phospholipase D-catalyzed transphosphatidylation of ethanol and glycerol, respectively. The transphosphatidylation by phospholipase D was stimulated in vitro by 12-O-tetradecanoylphorbol-13-acetate (TPA) and required the addition of ATP for an optimal response. GTP-gamma-S, an activator of G protein systems, also stimulated the process by an independent mechanism. It is postulated that the stimulation of phospholipid metabolism through phospholipase D activation represents an important mechanism whereby TPA might modulate intracellular signal generating systems or influence the activity of membrane-bound proteins by altering their lipid environment.