GENISTEIN INHIBITS POTENTIATION BY WORTMANNIN OF PROTEIN-KINASE C-ACTIVATED PHOSPHOLIPASE-D IN OSTEOBLAST-LIKE CELLS

We previously showed that protein kinase C (PKC) induces phosphatidylc holine-hydrolysing phospholipase D activation in osteoblast-like MC3T3 -E1 cells and that tyrosine kinase is involved in this activation. Wor tmannin, a potent inhibitor of phosphatidylinositol 3-kinase, markedly enhanced the formation of choline induced by 12-O-tetradecanoylphorbo l-13-acetate (TPA), an activator of PKC in MC3T3-E1 cells. The effect of wortmannin was dose-dependent between 0.1 mu M and 10 mu M. ML-7, a n inhibitor of myosin light chain kinase, had little effect on the TPA -induced formation of choline. Genistein, an inhibitor of protein tyro sine kinases, significantly suppressed the potentiation by wortmannin. These results strongly suggest that phosphatidylinositol 3-kinase is involved in the regulation of phospholipase D activation by PKC in ost eoblast-like cells.