Inhibition of PDGF-induced phospholipase D but not phospholipase C activation by herbimycin A

Abstract

It is known that PDGF-induced phospholipase D (PLD) activation occurs downstream of phospholipase Cγ1 (PLC-γ1) 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-γ1 activation and significantly reduced PDGF-induced tyrosine phosphorylations of 40-46 kD and 60 kD proteins in PLC-γ1-overexpressing NIH 3T3γ1 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.