title: Potential role of protein phosphorylation in GTP-gamma-S-dependent activation of phospholipase D.
abstract: Mammalian phospholipase D (PLD) is known to require nearly absolutely guanosine 5'-Q-3-thiotriphosphate (GTP-gamma-S) and a small G-protein for its activation. In streptolysin-Q-permeabilized HL-60 cells, phorbol ester or diacylglycerol enhanced greatly this PLD activation in the presence of ATP-Mg2+. Non-hydrolysable ATP analogue was inactive. This phorbol-ester-induced PLD activation was completely counteracted not only by protein kinase C (PKC) inhibitors but also by tyrosine kinase inhibitors. In cell-free lysates, the GTP-gamma-S-dependent activation of PLD was stimulated by ATP-Mg2+. This stimulation by ATP-Mg2+ did not respond to phorbol ester nor was it inhibited by PKC inhibitors, but was fully restrained by tyrosine kinase inhibitors. The results suggest that protein phosphorylation reactions by PKC and tyrosine kinase may take part, possibly in this order, in the small G-protein-coupled PLD activation.
authors.affiliation: Department of Biochemistry, Kobe University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: K
authors.initials: K
authors.lastname: Shimooku
authors.forename: T
authors.initials: T
authors.lastname: Akisue
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D019833:Genistein; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D007529:Isoflavones; D047428:Protein Kinase Inhibitors; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate; D019833:Genistein; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate