The DOI matches its Crossref record; 29 of the 30 references it cites were found in a registry or an index.
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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Cites
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677
Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway
Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V., & Benzer, S. (2004) · Current Biology · doi:10.1016/j.cub.2004.03.059 · Cited by 1,293
Regulation of protein kinase cascades by protein phosphatase 2A
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mTOR, translation initiation and cancer
Mamane, Y., Petroulakis, E., LeBacquer, O., & Sonenberg, N. (2006) · Oncogene · doi:10.1038/sj.onc.1209888 · Cited by 607
Ends-out, or replacement, gene targeting in Drosophila
Gong, W. J., & Golic, K. G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0535280100 · Cited by 363
Insulin-Like Signaling, Nutrient Homeostasis, and Life Span
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PP2A: Unveiling a Reluctant Tumor Suppressor
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Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks
Magnuson, B., Ekim, B., & Fingar, D. C. (2012) · Biochemical Journal · doi:10.1042/bj20110892 · Cited by 1,015
Regulation of TORC1 in Response to Amino Acid Starvation via Lysosomal Recruitment of TSC2
Demetriades, C., Doumpas, N., & Teleman, A. A. (2014) · Cell · doi:10.1016/j.cell.2014.01.024 · Cited by 414
Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia
Gutierrez, A., Pan, L., Groen, R. W. J., Baleydier, F., Kentsis, A., Marineau, J., Grebliunaite, R., Kozakewich, E., Reed, C., Pflumio, F., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci65093 · Cited by 220
Hales, E. C., Taub, J. W., & Matherly, L. H. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.09.021 · Cited by 187
Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes
Moraru, A., Wiederstein, J. L., Pfaff, D. H., Fleming, T. H., Miller, A. K., Nawroth, P. P., & Teleman, A. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.003 · Cited by 170
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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