Further evidence that the inhibition of glycogen synthase kinase-3beta by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216 - PubMed (original) (raw)

Further evidence that the inhibition of glycogen synthase kinase-3beta by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216

M Shaw et al. FEBS Lett. 1997.

Free article

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.

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