Phospholipase D, tumor promoters, proliferation and prostaglandins

Phosphatidylcholine hydrolysis by phospholipase D is a widespread response to cellular stimulation. However, the downstream signaling events subsequen t to phosphatidylcholine hydrolysis are just beginning to be determined. In itially it was proposed that diglyceride formation by phospholipase D and p hosphatidate phosphohydrolase resulted in long-term stimulation of protein kinase C. However, recent studies indicate that phosphatidic acid is the re levant signaling molecule in some signaling pathways. The present review wi ll summarize studies of phospholipase D in the response of cells to the tum or promoter 12-O-tetradecanoyl-phorbol-13-acetate, which causes cells to mi mic the phenotype of oncogenic transformation. The role of phospholipase D in stimulation of Raf-1 and prostaglandin H synthase type-2 is emphasized. (C) 1999 Elsevier Science B.V. All rights reserved.