Wortmannin has opposite effects on phorbol ester-induced DNA synthesis and phosphatidylcholine hydrolysis

AbstractThe 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 (P13K), 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