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 concentrati on dependent manner. Mesangial cells overexpressing the tyrosine kinas e pp60(c-src) (c-Src) were used to determine the effect of this non tr ansforming protooncogene on PLD activation. Overexpression of c-Src in terfered with PDGF-BB-mediated activation of PLD. This modulation was dependent on the tyrosine kinase activity of c-Src, since overexpressi on of tyrosine kinase-negative mutants of c-Src did not affect PLD act ivation. 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 inte rfered with PDGF-mediated but not with ATP- or GTP gamma S-mediated PL D activation.