Activation of phosphatidylcholine-specific phospholipase D (PC-PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA). Insulin activates the PLD-dependent hydrolysis of PC in plasma membranes of adipocytes by a mechanism that may involve wortmannin-sensitive phosphatidylinositol 3-kinase. In addition to the transient activation by growth factors stimulation, PC-PLD is constitutively activated in some of the Src- and Ras-transformed cells. PC-PLD is one of the target enzymes of ischemia; its decrease may cause a perturbation of PC hydrolysis and/or disorders of intracellular signal transduction or choline metabolism for acetylcholine formation in the brain.