Abstract
Involvement of Akt/Protein kinase B (PKB), a serine/threonine kinase with a pleckstrin-homology domain, in angiotensin II (ANG II)-induced signal transduction was investigated in cultured vascular smooth muscle cells (VSMC). Stimulation of the cells with ANG II led to a marked increase in the kinase activity of Akt/PKB, which coincided with Ser-473 phosphorylation. ANG II-stimulated Akt/PKB activation was rapid, concentration dependent, and inhibited by the AT1-receptor antagonist CV-11974, but not by pertussis toxin. Akt/PKB activity was stimulated by the Ca2+ ionophore ionomycin, suggesting the possible involvement of Ca2+ in ANG II-stimulated Akt/PKB activation. However, blockade of Ca2+ mobilization by BAPTA-AM only partially inhibited ANG II-stimulated Akt/PKB activation. ANG II-stimulated Akt/PKB activation was inhibited by the tyrosine kinase inhibitors genistein and herbimycin A and by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY-294002. These results indicate that ANG II stimulates Akt/PKB activity via AT1 receptors in VSMC and that the activities of tyrosine kinase and PI3K are required for this activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II / pharmacology*
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Angiotensin Receptor Antagonists
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Animals
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Cells, Cultured
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Chelating Agents / pharmacology
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Dose-Response Relationship, Drug
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / enzymology*
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Pertussis Toxin
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Platelet-Derived Growth Factor / pharmacology
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Protein Serine-Threonine Kinases*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Rats
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Tetradecanoylphorbol Acetate / pharmacology
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Time Factors
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Virulence Factors, Bordetella / pharmacology
Substances
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Angiotensin Receptor Antagonists
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Chelating Agents
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Enzyme Inhibitors
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Ionophores
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Phosphoinositide-3 Kinase Inhibitors
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins
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Virulence Factors, Bordetella
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Angiotensin II
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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Egtazic Acid
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Ionomycin
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Pertussis Toxin
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Protein-Tyrosine Kinases
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Tetradecanoylphorbol Acetate