Abstract
293 cells were transfected with wild-type GSK3beta (WT-GSK3beta) or a mutant in which the PKB phosphorylation site (Ser-9) was altered to Ala (A9-GSK3beta). Upon stimulation with IGF-1 or insulin, WT-GSK3beta was inhibited 75% or 60%, respectively, whereas the activity of the A9-GSK3beta mutant was unaffected. Incubation of WT-GSK3beta with PP2A1 (a Ser/Thr-specific phosphatase) completely reversed the IGF-1- or insulin-induced inhibition. IGF-1 stimulation did not induce any tyrosine dephosphorylation of WT-GSK3beta or A9-GSK3beta. Coexpression of WT-GSK3beta in 293 cells with either PKB alpha (also known as AKT) or PDK1 (the 'upstream' activator of PKB) mimicked the IGF-1- or insulin-induced phosphorylation of Ser-9 and inactivation of GSK3beta.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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Alanine
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Amino Acid Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Calcium-Calmodulin-Dependent Protein Kinases / biosynthesis
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Cell Line
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Humans
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Insulin / pharmacology
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Insulin-Like Growth Factor I / pharmacology*
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Isoenzymes / metabolism
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Mutagenesis, Site-Directed
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Phosphoprotein Phosphatases / metabolism
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Phosphorylation
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Phosphoserine / metabolism
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Phosphotyrosine / metabolism
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Protein Serine-Threonine Kinases / metabolism*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / biosynthesis
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Serine*
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Transfection
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Tyrosine*
Substances
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Insulin
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Isoenzymes
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Recombinant Proteins
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Phosphoserine
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Phosphotyrosine
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Tyrosine
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Serine
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Insulin-Like Growth Factor I
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Glycogen Synthase Kinases
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3-Phosphoinositide-Dependent Protein Kinases
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PDPK1 protein, human
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
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Phosphoprotein Phosphatases
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Alanine