Abstract
Akt is activated by growth factors to regulate various aspects of vascular smooth muscle cell function. Platelet-derived growth factor (PDGF) and insulin-like growth factor-1 activated Akt in vascular smooth muscle cells with a rapid reduction of total Akt protein that lasted for several hours. The downregulation of Akt required phosphatidylinositol 3-kinase activity, but not intrinsic Akt activity. The downregulation of Akt was abrogated by MG-132, a proteasome inhibitor, but not by inhibitors of calpain or cathepsins. Akt was found in ubiquitin immune complex after PDGF treatment. Proteasome-dependent degradation of Akt may provide a counter-regulatory mechanism against overactivation of Akt.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cysteine Endopeptidases / metabolism*
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Down-Regulation / drug effects
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Enzyme Inhibitors / pharmacology
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Growth Substances / pharmacology*
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Insulin-Like Growth Factor I / pharmacology
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Kinetics
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Male
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Multienzyme Complexes / metabolism*
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Muscle, Smooth, Vascular / cytology*
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Muscle, Smooth, Vascular / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Platelet-Derived Growth Factor / pharmacology
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Proteasome Endopeptidase Complex
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Protein Serine-Threonine Kinases*
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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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Rats, Wistar
Substances
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Enzyme Inhibitors
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Growth Substances
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Multienzyme Complexes
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Platelet-Derived Growth Factor
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Proto-Oncogene Proteins
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Insulin-Like Growth Factor I
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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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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex