Clk2 and B56β mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt
Open accessAbstract
Akt mediates important cellular decisions involved in growth, survival, and metabolism. The mechanisms by which Akt is phosphorylated and activated in response to growth factors or insulin have been extensively studied, but the molecular regulatory components and dynamics of Akt attenuation are poorly understood. Here we show that a downstream target of insulin-induced Akt activation, Clk2, triggers Akt dephosphorylation through the PP2A phosphatase complex. Clk2 phosphorylates the PP2A regulatory subunit B56β (PPP2R5B, B'β), which is a critical regulatory step in the assembly of the PP2A holoenzyme complex on Akt leading to dephosphorylation of both S473 and T308 Akt sites. Since Akt plays a pivotal role in cellular signaling, these results have important implications for our understanding of Akt regulation in many biological processes.
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B56β dephosphorylates AKT at both Thr308 and Ser473 and helps attenuate insulin signaling.
“More recent work has shown that B56β also targets AKT for dephosphorylation on both Thr308 and Ser473, facilitating the attenuation of insulin signaling (Rodgers et al., 2011).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Rodgers et al., 2011
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- Authors
- Rodgers, J. T., Vogel, R. O., & Puigserver, P.
- Affiliations
- Harvard University (US)
- Corresponding author
- Puigserver, Pere
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 41
- Issue
- 4
- Pages
- 471-479
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3060660
- OpenAlex
- W2053382318
- Cited by
- 99
- References
- 32
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 8 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 5
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- American Heart Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089883, R01DK069966)
- 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 › Metabolism, Diabetes, and Cancer
- Keywords
- CLK2, protein phosphatase 2A, Akt dephosphorylation, insulin signaling, protein phosphatase
- MeSH terms
- Animals, Cells, Cultured, Humans, Insulin, Male, Membrane Proteins, Mice, Inbred BALB C, Protein-Tyrosine Kinases, Transfection, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Mice, Protein Phosphatase 2
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