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 phospholipase C gamma 1 (PLC-gamma 1) activation. Herbimycin A, a specific inhibitor of Src family tyrosine kinase, dose-dependently inhibited PDGF-induced PLD activation (IC50 of 8 micrograms/ml) without affecting PLC-gamma 1 activation and significantly reduced PDGF-induced tyrosine phosphorylations of 40-46 kD and 60 kD proteins in PLC-gamma 1-overexpressing NIH 3T3 gamma 1 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.