Wortmannin has opposite effects on phorbol ester-induced DNA synthesis and phosphatidylcholine hydrolysis.
The tumor promoter phorbol 12-myristate 13-acetate (PMA) and hormonal activators of protein kinase C (PKC) commonly stimulate phospholipase D (PLD)-mediated formation of phosphatidic acid from phosphatidylcholine (PtdCho) in fibroblasts and other cell types. On the basis that phosphatidic acid is a mitogen, PLD is often considered to have a major role in the regulation of cell growth by PKC activators. However, we found that in NIH 3T3 fibroblasts wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), strongly inhibited DNA synthesis induced by 100 nM PMA, while it actually enhanced PMA-stimulated PtdCho hydrolysis. These results indicate that stimulation of PLD activity is either not required or not sufficient for the mitogenic action of PMA.
Kiss
Z
Z
Hormel Institute, University of Minnesota, Austin 55912, USA.
Tomono
M
M
D016475:3T3 Cells; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D020404:Glycerophospholipids; D006868:Hydrolysis; D051379:Mice; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010739:Phospholipase D / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D000077191:Wortmannin
D000730:Androstadienes; D020404:Glycerophospholipids; D010169:Palmitic Acids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; C051521:phosphatidylethanol; D019308:Palmitic Acid; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin