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Evidence for cell cycle-dependent, rapamycin-resistant phosphorylation of ribosomal protein S6 at S240/244

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Abstract

The ribosomal protein S6 is essential for the formation of the subunits of higher eukaryotic ribosomes, and S6 heterozygosity leads to early embryonal lethality in mice. S6 is phosphorylated at clustered residues S235/236 and S240/244 upon numerous physiological and pathological stimuli. So far, the S6Kinases, S6K1 and S6K2 are the only proven S6 S240/244 phosphorylating enzymes in mammalian cells. The activity of these S6Kinases is strictly regulated via the mammalian target of rapamycin (mTOR) enzyme complex with raptor, named mTORC1. In time course experiments with the mTORC1 inhibitor rapamycin we here demonstrate rapamycin-resistant phosphorylation of the ribosomal protein S6 at S240/244. Serum-restimulation experiments further demonstrated that this rapamycin-resistant S6 240/244 phosphorylation is induced via serum factors in a cell cycle-dependent manner. Our data allow new insights into the regulation of S6 phosphorylation and provide evidence for the existence of rapamycin-resistant S6 phosphorylating kinase activities.

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References

  • Bhaskar PT, Hay N (2007) The two TORCs and Akt. Dev Cell 12:487–502

    Article  CAS  PubMed  Google Scholar 

  • Burgstaller S, Rosner M, Lindengrün C, Hanneder M, Siegel N, Valli A, Fuchs C, Hengstschläger M (2008) Tuberin, p27 and mTOR in different cells. Amino Acids 36:297–302

    Article  PubMed  Google Scholar 

  • Chung J, Kuo CJ, Crabtree GR, Blenis J (1992) Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 69:1227–1236

    Article  CAS  PubMed  Google Scholar 

  • Dann SG, Selvaraj A, Thomas G (2007) mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer. Trends Mol Med 13:252–259

    Article  CAS  PubMed  Google Scholar 

  • Laplante M, Sabatini DM (2009) mTOR signaling at a glance. J Cell Sci 122:3589–3594

    Article  CAS  PubMed  Google Scholar 

  • Meyuhas O (2008) Physiological roles of ribosomal protein S6: one of its kind. Int Rev Cell Mol Biol 268:1–37

    Article  CAS  PubMed  Google Scholar 

  • Rosner M, Hengstschläger M (2007) Cytoplasmic/nuclear localization of tuberin in different cell lines. Amino Acids 33:575–579

    Article  CAS  PubMed  Google Scholar 

  • Rosner M, Hengstschläger M (2008) Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Hum Mol Genet 17:2934–2948

    Article  CAS  PubMed  Google Scholar 

  • Rosner M, Freilinger A, Hengstschläger M (2004) Proteins interacting with the tuberous sclerosis gene products. Amino Acids 27:119–128

    Article  CAS  PubMed  Google Scholar 

  • Rosner M, Freilinger A, Hanneder M, Fujita N, Lubec G, Tsuruo T, Hengstschläger M (2007) p27Kip1 localization depends on the tumor suppressor protein tuberin. Hum Mol Genet 16:1541–1556

    Article  CAS  PubMed  Google Scholar 

  • Rosner M, Hanneder M, Siegel N, Valli A, Fuchs C, Hengstschläger M (2008) The mTOR pathway and its role in human genetic diseases. Mutat Res 659:284–292

    Article  CAS  PubMed  Google Scholar 

  • Rosner M, Fuchs C, Siegel N, Valli A, Hengstschläger M (2009) Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle. Hum Mol Genet 17:3298–3310

    Article  Google Scholar 

  • Rosner M, Siegel N, Valli A, Fuchs C, Hengstschläger M (2010) mTOR phosphorylated at S2448 binds to raptor and rictor. Amino Acids 38:223–228

    Article  CAS  PubMed  Google Scholar 

  • Roux PP, Shahbazian D, Vi H, Holz MK, Cohen MS, Taunton J, Sonenberg N, Blenis J (2007) RAS/ERK signalling promotes site-specific ribosomal protein S6 phosphorylation via RSK and stimulates Cap-dependent translation. J Biol Chem 282:14056–14064

    Article  CAS  PubMed  Google Scholar 

  • Ruvinsky I, Meyuhas O (2006) Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Trends Biochem Sci 31:342–346

    Article  CAS  PubMed  Google Scholar 

  • Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM (2006) Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22:159–168

    Article  CAS  PubMed  Google Scholar 

  • Shaw RJ, Cantley LC (2006) Ras, PI(3)K and mTOR signalling controls tumor growth. Nature 441:424–430

    Article  CAS  PubMed  Google Scholar 

  • Yang Q, Guan K-L (2007) Expanding mTOR signaling. Cell Res 17:666–681

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Research in our laboratory is supported via grants from the Herzfelder’sche Familienstiftung and from the Österreichische Nationalbank.

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  1. Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, 1090, Vienna, Austria

    M. Rosner & M. Hengstschläger

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  1. M. Rosner
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  2. M. Hengstschläger
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Correspondence to M. Hengstschläger.

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Rosner, M., Hengstschläger, M. Evidence for cell cycle-dependent, rapamycin-resistant phosphorylation of ribosomal protein S6 at S240/244. Amino Acids 39, 1487–1492 (2010). https://doi.org/10.1007/s00726-010-0615-2

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  • DOI: https://doi.org/10.1007/s00726-010-0615-2

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