Further evidence that the inhibition of glycogen synthase kinase‐3β by IGF‐1 is mediated by PDK1/PKB‐induced phosphorylation of Ser‐9 and not by …
293 cells were transfected with wild‐type GSK3β (WT‐GSK3β) or a mutant in which the PKB
phosphorylation site (Ser‐9) was altered to Ala (A9‐GSK3β). Upon stimulation with IGF‐1 or
insulin, WT‐GSK3β was inhibited 75% or 60%, respectively, whereas the activity of the A9‐
GSK3β mutant was unaffected. Incubation of WT‐GSK3β 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‐GSK3β or A9‐GSK3β …
phosphorylation site (Ser‐9) was altered to Ala (A9‐GSK3β). Upon stimulation with IGF‐1 or
insulin, WT‐GSK3β was inhibited 75% or 60%, respectively, whereas the activity of the A9‐
GSK3β mutant was unaffected. Incubation of WT‐GSK3β 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‐GSK3β or A9‐GSK3β …
293 cells were transfected with wild‐type GSK3β (WT‐GSK3β) or a mutant in which the PKB phosphorylation site (Ser‐9) was altered to Ala (A9‐GSK3β). Upon stimulation with IGF‐1 or insulin, WT‐GSK3β was inhibited 75% or 60%, respectively, whereas the activity of the A9‐GSK3β mutant was unaffected. Incubation of WT‐GSK3β 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‐GSK3β or A9‐GSK3β. Coexpression of WT‐GSK3β in 293 cells with either PKBα (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 GSK3β.
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