Phospholipase D,tumor promoters,proliferation and prostaglandins

Phosphatidylcholine hydrolysis by phospholipase D is a widespread response to cellular stimulation. However, the downstream signaling events subsequent to phosphatidylcholine hydrolysis are just beginning to be determined. Initially it was proposed that diglyceride formation by phospholipase D and phosphatidate phosphohydrolase resulted in long-term stimulation of protein kinase C. However, recent studies indicate that phosphatidic acid is the relevant signaling molecule in some signaling pathways. The present review will summarize studies of phospholipase D in the response of cells to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate, which causes cells to mimic the phenotype of oncogenic transformation. The role of phospholipase D in stimulation of Raf-1 and prostaglandin H synthase type-2 is emphasized.