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.
Kim
B Y
BY
Korea Research Institute of Bioscience and Biotechnology, Yuseong, Taejon, Korea.
Ahn
S C
SC
Oh
H K
HK
Lee
H S
HS
Mheen
T I
TI
Rho
H M
HM
Ahn
J S
JS
D016475:3T3 Cells; D000818:Animals; D016227:Benzoquinones; D004789:Enzyme Activation / Q000187:drug effects; D047029:Lactams, Macrocyclic; D051379:Mice; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D010982:Platelet-Derived Growth Factor; D011809:Quinones; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D010739:Phospholipase D