Modulation of phospholipase D stimulation in c-src transfected mesangial cells.
Stimulation of rat mesangial cells with platelet-derived growth factor BB (PDGF-BB) enhanced phospholipase D (PLD) activity in a concentration dependent manner. Mesangial cells overexpressing the tyrosine kinase pp60c-src (c-Src) were used to determine the effect of this non transforming protooncogene on PLD activation. Overexpression of c-Src interfered with PDGF-BB-mediated activation of PLD. This modulation was dependent on the tyrosine kinase activity of c-Src, since overexpression of tyrosine kinase-negative mutants of c-Src did not affect PLD activation. No effect of c-Src overexpression was observed, when PLD was activated by ATP or guanosine 5'-3-O-(thio)triphosphate (GTP gamma S). The results indicate that the tyrosine kinase c-Src specifically interfered with PDGF-mediated but not with ATP- or GTP gamma S-mediated PLD activation.
Reiser
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Medizinische Klinik IV, Universität Erlangen-Nürnberg, Germany.
Goppelt-Struebe
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D002455:Cell Division; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000201:enzymology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D010739:Phospholipase D / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D014162:Transfection
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000255:Adenosine Triphosphate; D016392:Proto-Oncogene Proteins pp60(c-src); D010739:Phospholipase D; D019204:GTP-Binding Proteins