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PP2A regulatory subunit PP2A-B' counteracts S6K phosphorylation
Open accessAbstract
The insulin/TOR signaling pathway plays a crucial role in animal homeostasis, sensing nutrient status to regulate organismal growth and metabolism. We identify here the Drosophila B' regulatory subunit of PP2A (PP2A-B') as a novel, conserved component of the insulin pathway that specifically targets the PP2A holoenzyme to dephosphorylate S6K. PP2A-B' knockout flies have elevated S6K phosphorylation and exhibit phenotypes typical of elevated insulin signaling such as reduced total body triglycerides and reduced longevity. We show that PP2A-B' interacts with S6K both physically and genetically. The human homolog of PP2A-B', PPP2R5C, also counteracts S6K1 phosphorylation, indicating a conserved mechanism in mammals. Since S6K affects development of cancer and metabolic disease, our data identify PPP2R5C as a novel factor of potential medical relevance.
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“Activation of p70S6K is mediated by sequential phosphorylation on multiple sites by mTOR and PDK1, which is counteracted by PP2A/B56γ (Hahn et al., 2010; Jastrzebski et al., 2007).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Hahn et al., 2010
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Metadata
- Authors
- Hahn, K., Miranda, M., Francis, V. A., Vendrell, J., Zorzano, A., & Teleman, A. A.
- Affiliations
- German Cancer Research Center (DE)
- Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (ES)
- Corresponding author
- Teleman, Aurelio A.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 11
- Issue
- 5
- Pages
- 438-444
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2061893502
- Cited by
- 131
- References
- 30
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 11 · 2021: 9 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 11 · 2016: 12 · 2015: 10 · 2014: 11 · 2013: 6 · 2012: 9
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- 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 › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein phosphatase 2A, S6K phosphorylation, S6K1, PPP2R5C, protein dephosphorylation, Drosophila, longevity, triglycerides, TOR signaling, protein-protein interaction
- MeSH terms
- Animals, Drosophila, Humans, Insulin, Longevity, Phosphoprotein Phosphatases, Phosphorylation, Triglycerides, Signal Transduction, Drosophila Proteins, Ribosomal Protein S6 Kinases, 70-kDa, Protein Phosphatase 2, Gene Knockout Techniques
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