FEBS Letters · 1997 · 234 citations · 23 references
Life SciencesBiochemistryCell BiologyCell SignalingMetabolismSignal TransductionGrowth Factor SignalingProtein Kinase CascadesGlycogen Synthase Kinase 3 RegulationGlycogen Synthase Kinase 3 SignalingGlycogen Synthase Kinase RegulationInsulin SignalingPhosphatase InhibitionPhosphoinositide 3-Kinase-akt ActivationProtein DephosphorylationProtein Kinase B Signaling
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.
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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Darren A.E. Cross, Dario R. Alessi, Philip Cohen et al. · Nature · 1995 · 5.2K citations
Mechanism of activation of protein kinase B by insulin and IGF‐1.
Dario R. Alessi, Mirjana Andjelković, B. Caudwell et al. · The EMBO Journal · 1996 · 3K citations · Full text