Tyrosine kinase regulates phospholipase D activation at a point downstream from protein kinase C in osteoblast-like cells.
It has recently been shown that the activation of protein kinase C (PKC) induces protein tyrosine phosphorylation in osteoblast-like MC3T3-E1 cells. We previously reported that the activation of PKC stimulates phosphatidylcholine-hydrolyzing phospholipase D in these cells. In this study, we examined whether protein tyrosine kinase is involved in the PKC-induced activation of phospholipase D in MC3T3-E1 cells. Genistein, an inhibitor of protein tyrosine kinases, which by itself had little effect on choline formation, significantly suppressed the formation of choline induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, in a dose-dependent manner. Tyrphostin, an inhibitor of protein tyrosine kinases chemically distinct from genistein, also dose-dependently suppressed the TPA-induced formation of choline. Sodium orthovanadate, an inhibitor of protein tyrosine phosphatases, significantly enhanced the TPA-induced formation of choline in a dose-dependent manner. These results strongly suggest that protein tyrosine kinase regulates phospholipase D activity at a point downstream from PKC in osteoblast-like cells.
Kozawa
O
O
Department of Biochemistry, Institute for Developmental Research, Aichi Prefectural Colony, Japan.
Suzuki
A
A
Oiso
Y
Y
D016475:3T3 Cells; D000818:Animals; D000831:Animals, Newborn; D002396:Catechols / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology*; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012886:Skull; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020032:Tyrphostins; D014638:Vanadates / Q000494:pharmacology
D002396:Catechols; D007529:Isoflavones; D009570:Nitriles; D020032:Tyrphostins; C060152:tyrphostin 47; D014638:Vanadates; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D002794:Choline; D013755:Tetradecanoylphorbol Acetate