Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Benzoquinones
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Glycerophospholipids*
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Inositol Phosphates / biosynthesis
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Isoenzymes / metabolism
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Lactams, Macrocyclic
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Mice
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Phosphatidic Acids / biosynthesis
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Phospholipase C gamma
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Phospholipase D / metabolism
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Phosphoproteins / analysis
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Phosphorylation
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Platelet-Derived Growth Factor / pharmacology*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Quinones / pharmacology*
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Rifabutin / analogs & derivatives
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Tetradecanoylphorbol Acetate / pharmacology
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Type C Phospholipases / metabolism*
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Tyrosine / metabolism
Substances
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Benzoquinones
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Enzyme Inhibitors
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Glycerophospholipids
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Inositol Phosphates
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Isoenzymes
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Lactams, Macrocyclic
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Phosphatidic Acids
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Phosphoproteins
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Platelet-Derived Growth Factor
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Quinones
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phosphatidylethanol
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Rifabutin
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Tyrosine
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herbimycin
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Protein-Tyrosine Kinases
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Type C Phospholipases
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Phospholipase C gamma
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Phospholipase D
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Tetradecanoylphorbol Acetate