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 C gamma l (PLC-gamma l) activation. Herbimycin A, a specific inhibitor of Src family tyrosine kinase, dose-dependently inhibited PDGF-induced PLD activation (IC50 of 8 mu g/ml) without affecting PLC-gamma l activation and significantly reduced PDGF-induced tyrosine phosphorylations of 40-46 kD and 60 kD proteins in PLC-gamma l overexpressing NIH 3T3 gamma l 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. (C) 1995 Academic Press, Inc.