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 phosphatidylcholine-hydrolysing phospholipase D activation in osteoblast-like MC3T3-E1 cells and that tyrosine kinase is involved in this activation. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, markedly enhanced the formation of choline induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC in MC3T3-E1 cells. The effect of wortmannin was dose-dependent between 0.1 microM and 10 microM. ML-7, an inhibitor of myosin light chain kinase, had little effect on the TPA-induced formation of choline. Genistein, an inhibitor of protein tyrosine 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 osteoblast-like cells.
Kozawa
O
O
Department of Biochemistry, Institute for Developmental Research, Aichi, Japan.
Suzuki
A
A
Shinoda
J
J
Oiso
Y
Y
D016475:3T3 Cells; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D002794:Choline / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007529:Isoflavones; D019833:Genistein; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D002794:Choline; D013755:Tetradecanoylphorbol Acetate; D000077191:Wortmannin