Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B

Cross, Darren A. E.; Alessi, Dario R.; Cohen, Philip; Andjelkovich, Mirjana; Hemmings, Brian A.

doi:10.1038/378785a0

Cited by 5,244PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingWnt/β-catenin signaling in development and cancer

Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B

Cross, Darren A. E., Alessi, Dario R., Cohen, Philip, Andjelkovich, Mirjana, Hemmings, Brian A.·1995·Nature

DOI 10.1038/378785a0

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Abstract

Glycogen synthase kinase-3 (GSK3) is implicated in the regulation of several physiological processes, including the control of glycogen and protein synthesis by insulin, modulation of the transcription factors AP-1 and CREB, the specification of cell fate in Drosophila and dorsoventral patterning in Xenopus embryos. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k). Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase.

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The PI3K pathway is activated by insulin, which leads to the inhibition of GSK-3β activity via phosphorylation of its serine-9 residue by AKT/PKB.
“The PI3K pathway is activated by insulin, which leads to the inhibition of GSK-3β activity via phosphorylation of its serine-9 residue by AKT/PKB (108,109).”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [108]

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Authors: Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A.
Affiliations: University of Dundee (GB)
Friedrich Miescher Institute (CH)
ORCID: Cross, Darren A. E.
Alessi, Dario R.
Cohen, Philip
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1995-12
Volume: 378
Issue: 6559
Pages: 785-789
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/378785a0
OpenAlex: W2058138221
Cited by: 5,244
References: 2
Citations by year: 2026: 63 · 2025: 79 · 2024: 102 · 2023: 135 · 2022: 149 · 2021: 144 · 2020: 151 · 2019: 159 · 2018: 157 · 2017: 179 · 2016: 188 · 2015: 215 · 2014: 246 · 2013: 252 · 2012: 263
FWCI: 27.13
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Keywords: glycogen synthase kinase-3, insulin signaling, Akt, GSK3 inhibition, serine phosphorylation, p70 S6 kinase, phosphatidylinositol 3-kinase, glycogen synthesis, protein synthesis
MeSH terms: Amino Acid Sequence, Animals, Cells, Cultured, Enzyme Activation, Microtubule-Associated Proteins, Molecular Sequence Data, Muscles, Phosphorylation, Proto-Oncogene Proteins, Serine, 3T3 Cells, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Ribosomal Protein S6 Kinases, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, Mice

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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B

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