Inhibition of PDGF-Induced Phospholipase D but Not Phospholipase C Activation by Herbimycin A

It is known that PDGF-induced phospholipase D (PLD) activation occurs downstream of phosphlipase Cγl (PLC-γl) activation. Herbimycin A, a specific inhibitor of Src family tyrosine kinase, dose-dependently inhibited PDGF-induced PLD activation (IC50 of 8 μg/ml) without affecting PLC-γl activation and significantly reduced PDGF-induced tyrosine phosphorylations of 40-46 kD and 60 kD proteins in PLC-γl- overexpressing NIH 3T3γl cells. These results suggest that PLC activation is necessary but not sufficient for PDGF-induced PLD activation. Tyrosine phosphorylation of p40-p46 and p60 is thought to be involved in PDGF-induced activation of PLD but not of PLC.