Inhibition of PDGF-induced phospholipase C activation by herbimycin A.
Herbimycin A, an inhibitor of protein tyrosine kinases, dose-dependently reduced PDGF-induced inositol phosphates (IPt) accumulation without effect on phosphatidylethanol (PEt) formation in PLC-gamma 1-overexpressing NIH 3T3 (NIH 3T3 gamma 1) cells. The compound also reduced tyrosine phosphorylations of some proteins including PLC-gamma 1 in response to PDGF. On the other hand, phorbol 12-myristate 13-acetate (PMA)-induced phospholipase D (PLD) activation was reduced by herbimycin A in the cells, indicating that the pathways for PLD activation by PDGF and PMA are different from each other. Also, these results suggest that PLC-gamma 1 activation is not always an upstream event for PLD activation and that tyrosine phosphorylation of one or more proteins not affected by herbimycin A should be indispensable for PLD activation in PDGF-stimulated NIH 3T3 gamma 1 cells.
Kim
B Y
BY
Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Taejon, South Korea.
Ahn
S C
SC
Kang
D O
DO
Ko
H R
HR
Oh
W K
WK
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; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020404:Glycerophospholipids; D007295:Inositol Phosphates / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D047029:Lactams, Macrocyclic; D051379:Mice; D010712:Phosphatidic Acids / Q000096:biosynthesis; D051966:Phospholipase C gamma; D010739:Phospholipase D / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D020404:Glycerophospholipids; D007295:Inositol Phosphates; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D010712:Phosphatidic Acids; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011809:Quinones; C051521:phosphatidylethanol; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate