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

被引：212
作者：
Shaw, M
Cohen, P
Alessi, DR
机构：
[1] MRC Protein Phosphorylation Unit, Dept. of Biochem., Univ. of Dundee
来源：
FEBS LETTERS | 1997年 / 416卷 / 03期
基金：
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词：
insulin; insulin-like growth factor-1; protein kinase B; glycogen synthase kinase-3; glycogen synthase; 3-phosphoinositide-dependent protein kinase;
D O I：
10.1016/S0014-5793(97)01235-0
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
293 cells were transfected with mild-type GSK3 beta (WT-GSK3 beta) or a mutant in which the PKB phosphorylation site (Ser-9) mas altered to Ala (A9-GSK3 beta), Upon stimulation with IGF-1 or insulin, WT-GSK3 beta was inhibited 75% or 60%, respectively, whereas the activity of the A9-GSK3 beta mutant was unaffected, Incubation of WT-GSK3 beta with PP2A(1) (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-GSK3 beta or A9-GSK3 beta, Coexpression of WT-GSK3 beta 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 GSK3 beta. (C) 1997 Federation of European Biochemical Societies.
引用
收藏
页码：307 / 311
页数：5
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