Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase‐3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin
Abstract
Eukaryotic initiation factor eIF2B catalyses a key regulatory step in mRNA translation. eIF2B and total protein synthesis are acutely activated by insulin, and this requires phosphatidylinositol 3‐kinase (PI 3‐kinase). The ϵ‐subunit of eIF2B is phosphorylated by glycogen synthase kinase‐3 (GSK‐3), which is inactivated by insulin in a PI 3‐kinase‐dependent manner. Here we identify the phosphorylation site in eIF2Bϵ as Ser 540 and show that treatment of eIF2B with GSK‐3 inhibits its activity. Ser 540 is phosphorylated in intact cells and undergoes dephosphorylation in response to insulin. This is blocked by PI 3‐kinase inhibitors. Insulin‐induced dephosphorylation of this inhibitory site in eIF2B seems likely to be important in the overall activation of translation by this hormone.
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GSK-3β is a major regulator of protein synthesis through its actions on eIF2B.
“It is also a major regulator of protein synthesis through its actions on eIF2B (568).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [568]
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- Authors
- Welsh, G. I., Miller, C. M., Loughlin, A. J., & Price, N. T.
- Affiliations
- University of Kent (GB)
- University of Bristol (GB)
- ORCID
- Welsh, Gavin I
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1998-01-09
- Volume
- 421
- Issue
- 2
- Pages
- 125-130
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2057327606
- Cited by
- 298
- References
- 39
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 17 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 7 · 2013: 16 · 2012: 19
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Open Research Online (The Open University) (submittedVersion)
- Funders
- Wellcome Trust
- 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 › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- eIF2B, glycogen synthase kinase-3, dephosphorylation, insulin signaling, phosphatidylinositol 3-kinase, mRNA translation regulation, protein synthesis
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Cricetinae, Insulin, Molecular Sequence Data, Phosphorylation, Rabbits, Serine, Eukaryotic Initiation Factor-2, CHO Cells, Conserved Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3
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