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 dephosphorylation of Tyr-216

Morag Shaw; Philip Cohen; Dario R. Alessi

doi:10.1016/S0014-5793(97)01235-0

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 dephosphorylation of Tyr-216

Morag Shaw (Lead / Corresponding author), Philip Cohen, Dario R. Alessi

MRC PPU

Research output: Contribution to journal › Article › peer-review

220 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	307-311
Number of pages	5
Journal	FEBS Letters
Volume	416
Issue number	3
DOIs	https://doi.org/10.1016/S0014-5793(97)01235-0
Publication status	Published - 27 Oct 1997

Keywords

3-Phosphoinositide-dependent protein kinase
Glycogen synthase
Glycogen synthase kinase-3
Insulin
Insulin-like growth factor-1
Protein kinase B

ASJC Scopus subject areas

Structural Biology
Biophysics
Biochemistry
Molecular Biology
Genetics
Cell Biology

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title = "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 dephosphorylation of Tyr-216",

abstract = "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.",

keywords = "3-Phosphoinositide-dependent protein kinase, Glycogen synthase, Glycogen synthase kinase-3, Insulin, Insulin-like growth factor-1, Protein kinase B",

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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 dephosphorylation of Tyr-216. / Shaw, Morag (Lead / Corresponding author); Cohen, Philip ; Alessi, Dario R.
In: FEBS Letters, Vol. 416, No. 3, 27.10.1997, p. 307-311.

Research output: Contribution to journal › Article › peer-review

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AU - Shaw, Morag

AU - Cohen, Philip

AU - Alessi, Dario R.

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AB - 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.

KW - 3-Phosphoinositide-dependent protein kinase

KW - Glycogen synthase

KW - Glycogen synthase kinase-3

KW - Insulin

KW - Insulin-like growth factor-1

KW - Protein kinase B

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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 dephosphorylation of Tyr-216

Abstract

Keywords

ASJC Scopus subject areas

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