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Gene Review

RPS6  -  ribosomal protein S6

Homo sapiens

Synonyms: 40S ribosomal protein S6, OK/SW-cl.2, Phosphoprotein NP33, S6
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Disease relevance of RPS6


High impact information on RPS6

  • Heat shock of cell suspension cultures of tomato (Lycopersicon peruvianum) results in a rapid and reversible decline of the phosphorylation level of a single basic ribosomal protein of the small subunit (tentatively identified as ribosomal protein S6) [6].
  • Two known Ras-regulated kinases were identified, phosphoinositide 3-kinase p110alpha and ribosomal protein S6 kinase p70(S6K1), plus the MAP kinase kinase kinase kinase MINK, which had not previously been implicated in Ras signaling [7].
  • Ribosomal protein S6 phosphorylation: from protein synthesis to cell size [8].
  • In addition to its role in glucose homeostasis in the whole mouse, phosphorylation of rpS6 is essential for regulating the size of at least some cell types, but is dispensable for translational control of mRNAs with a 5' terminal oligopyrimidine tract (TOP mRNAs) - its previously assigned targets [8].
  • Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region [9].

Chemical compound and disease context of RPS6


Biological context of RPS6


Anatomical context of RPS6

  • Drosophila S6K expressed in COS or NIH 3T3 cells phosphorylates mammalian RPS6 in a mitogen-dependent wortmannin- and rapamycin-sensitive manner, suggesting that its regulation is similiar to mammalian p70S6k [13].
  • The intron-containing gene encoding human ribosomal protein S6 (rpS6), the major phosphoprotein in the mammalian ribosome, has been cloned [11].
  • Furthermore, fetal hepatocyte proliferation was sustained even though rapamycin administration resulted in the dephosphorylation of ribosomal protein S6 [14].
  • We found that ribosomal protein S6 (S6), which exerts translational control of protein synthesis and is required for cell growth, is hyperphosphorylated in the smooth muscle-like cell lesions of LAM patients compared with smooth muscle cells from normal human blood vessels and trachea [15].
  • By screening the human HeLa cell cDNA library in lambda ZAPII vector (Stratagene, La Jolla, CA), we identified and sequenced a partially spliced pre mRNA copy of hRPS6 [16].

Associations of RPS6 with chemical compounds


Physical interactions of RPS6

  • Since mTOR activates both the 40S ribosomal protein S6 kinase ((p)70(s6k)) and the eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), RAP blocks activation of these downstream signaling elements, which results in cell cycle arrest in the G1 arrest [22].

Enzymatic interactions of RPS6


Regulatory relationships of RPS6


Other interactions of RPS6


Analytical, diagnostic and therapeutic context of RPS6


  1. Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition. Guerreiro, A.S., Boller, D., Shalaby, T., Grotzer, M.A., Arcaro, A. Int. J. Cancer (2006) [Pubmed]
  2. Frequent [corrected] hyperphosphorylation of ribosomal protein S6 [corrected] in lymphangioleiomyomatosis-associated angiomyolipomas. Robb, V.A., Astrinidis, A., Henske, E.P. Mod. Pathol. (2006) [Pubmed]
  3. Array-comparative genomic hybridization of central chondrosarcoma: identification of ribosomal protein S6 and cyclin-dependent kinase 4 as candidate target genes for genomic aberrations. Rozeman, L.B., Szuhai, K., Schrage, Y.M., Rosenberg, C., Tanke, H.J., Taminiau, A.H., Cleton-Jansen, A.M., Bovée, J.V., Hogendoorn, P.C. Cancer (2006) [Pubmed]
  4. Antigenic reactivity of ribosomal protein S6 and the calcium-binding ATPase inhibitor protein of mammalian mitochondria. Penner, C.G., Murphy, L.C., Huzel, N.J., Yamada, E.W. Mol. Cell. Biochem. (1991) [Pubmed]
  5. Activation of the pp90rsk and mitogen-activated serine/threonine protein kinases by ionizing radiation. Kharbanda, S., Saleem, A., Shafman, T., Emoto, Y., Weichselbaum, R., Kufe, D. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Heat-shock-induced alterations of ribosomal protein phosphorylation in plant cell cultures. Scharf, K.D., Nover, L. Cell (1982) [Pubmed]
  7. Involvement of MINK, a Ste20 family kinase, in Ras oncogene-induced growth arrest in human ovarian surface epithelial cells. Nicke, B., Bastien, J., Khanna, S.J., Warne, P.H., Cowling, V., Cook, S.J., Peters, G., Delpuech, O., Schulze, A., Berns, K., Mullenders, J., Beijersbergen, R.L., Bernards, R., Ganesan, T.S., Downward, J., Hancock, D.C. Mol. Cell (2005) [Pubmed]
  8. Ribosomal protein S6 phosphorylation: from protein synthesis to cell size. Ruvinsky, I., Meyuhas, O. Trends Biochem. Sci. (2006) [Pubmed]
  9. Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. Bärlund, M., Forozan, F., Kononen, J., Bubendorf, L., Chen, Y., Bittner, M.L., Torhorst, J., Haas, P., Bucher, C., Sauter, G., Kallioniemi, O.P., Kallioniemi, A. J. Natl. Cancer Inst. (2000) [Pubmed]
  10. Herpes simplex virus type-1-induced stimulation of ribosomal protein S6 phosphorylation is inhibited in neomycin-treated human epidermoid carcinoma 2 cells and in ras-transformed cells. Massé, T., Garcin, D., Jacquemont, B., Madjar, J.J. Eur. J. Biochem. (1990) [Pubmed]
  11. The organization of the intron-containing human S6 ribosomal protein (rpS6) gene and determination of its location at chromosome 9p21. Antoine, M., Fried, M. Hum. Mol. Genet. (1992) [Pubmed]
  12. Identification of phosphoprotein NP33 as a nucleus-associated ribosomal S6 protein and its phosphorylation in hematopoietic cells. Macfarlane, D.E., Gailani, D. Cancer Res. (1990) [Pubmed]
  13. A Drosophila gene structurally and functionally homologous to the mammalian 70-kDa s6 kinase gene. Watson, K.L., Chou, M.M., Blenis, J., Gelbart, W.M., Erikson, R.L. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  14. Ribosomal protein S6 phosphorylation and function during late gestation liver development in the rat. Boylan, J.M., Anand, P., Gruppuso, P.A. J. Biol. Chem. (2001) [Pubmed]
  15. Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). Goncharova, E.A., Goncharov, D.A., Eszterhas, A., Hunter, D.S., Glassberg, M.K., Yeung, R.S., Walker, C.L., Noonan, D., Kwiatkowski, D.J., Chou, M.M., Panettieri, R.A., Krymskaya, V.P. J. Biol. Chem. (2002) [Pubmed]
  16. The human ribosomal protein S6 gene: isolation, primary structure and location in chromosome 9. Pata, I., Hoth, S., Kruppa, J., Metspalu, A. Gene (1992) [Pubmed]
  17. Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. Kimball, S.R., Jefferson, L.S. J. Nutr. (2006) [Pubmed]
  18. Abnormal regulation of ribosomal protein S6 kinase by insulin in skeletal muscle of insulin-resistant humans. Sommercorn, J., Fields, R., Raz, I., Maeda, R. J. Clin. Invest. (1993) [Pubmed]
  19. Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. Ly, C., Arechiga, A.F., Melo, J.V., Walsh, C.M., Ong, S.T. Cancer Res. (2003) [Pubmed]
  20. Estrogen-Induced Activation of Mammalian Target of Rapamycin Is Mediated via Tuberin and the Small GTPase Ras Homologue Enriched in Brain. Yu, J., Henske, E.P. Cancer Res. (2006) [Pubmed]
  21. Monoclonal antibodies mimic insulin activation of ribosomal protein S6 kinase without activation of insulin receptor tyrosine kinase. Studies in cells transfected with normal and mutant human insulin receptors. Sung, C.K., Maddux, B.A., Hawley, D.M., Goldfine, I.D. J. Biol. Chem. (1989) [Pubmed]
  22. The molecular target of rapamycin (mTOR) as a therapeutic target against cancer. Mita, M.M., Mita, A., Rowinsky, E.K. Cancer Biol. Ther. (2003) [Pubmed]
  23. Ribosomal S6 kinase 2 inhibition by a potent C-terminal repressor domain is relieved by mitogen-activated protein-extracellular signal-regulated kinase kinase-regulated phosphorylation. Martin, K.A., Schalm, S.S., Romanelli, A., Keon, K.L., Blenis, J. J. Biol. Chem. (2001) [Pubmed]
  24. Functional characterization of a maize ribosomal S6 protein kinase (ZmS6K), a plant ortholog of metazoan p70(S6K). Reyes de la Cruz, H., Aguilar, R., Sánchez de Jiménez, E. Biochemistry (2004) [Pubmed]
  25. Death-associated protein kinase phosphorylates Mammalian ribosomal protein s6 and reduces protein synthesis. Schumacher, A.M., Velentza, A.V., Watterson, D.M., Dresios, J. Biochemistry (2006) [Pubmed]
  26. Rapamycin inhibits the phosphorylation of p70 S6 kinase in IL-2 and mitogen-activated human T cells. Terada, N., Lucas, J.J., Szepesi, A., Franklin, R.A., Takase, K., Gelfand, E.W. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  27. Regulation of ribosomal protein S6 kinase in human mammary tumor cells: effect of estrogen, growth factors and phorbol ester. Novak-Hofer, I., Küng, W., Fabbro, D., Matter, A., Eppenberger, U. Experientia (1988) [Pubmed]
  28. Regulation of ribosomal S6 kinase 2 by effectors of the phosphoinositide 3-kinase pathway. Martin, K.A., Schalm, S.S., Richardson, C., Romanelli, A., Keon, K.L., Blenis, J. J. Biol. Chem. (2001) [Pubmed]
  29. Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region. Gout, I., Minami, T., Hara, K., Tsujishita, Y., Filonenko, V., Waterfield, M.D., Yonezawa, K. J. Biol. Chem. (1998) [Pubmed]
  30. Activation of mammalian target of rapamycin signaling pathway contributes to tumor cell survival in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Vega, F., Medeiros, L.J., Leventaki, V., Atwell, C., Cho-Vega, J.H., Tian, L., Claret, F.X., Rassidakis, G.Z. Cancer Res. (2006) [Pubmed]
  31. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Schalm, S.S., Fingar, D.C., Sabatini, D.M., Blenis, J. Curr. Biol. (2003) [Pubmed]
  32. Regulated phosphorylation of 40S ribosomal protein S6 in root tips of maize. Williams, A.J., Werner-Fraczek, J., Chang, I.F., Bailey-Serres, J. Plant Physiol. (2003) [Pubmed]
  33. The activity of protein kinases from hamster fibroblasts towards a synthetic peptide based on a carboxy-terminal portion of ribosomal protein S6. Munro, J., Campbell, D.G., Leader, D.P. Biochim. Biophys. Acta (1990) [Pubmed]
  34. Molecular cloning, developmental expression, and phosphorylation of ribosomal protein S6 in the endocrine gland responsible for insect molting. Song, Q., Gilbert, L.I. J. Biol. Chem. (1997) [Pubmed]
  35. Platelet-derived growth factor stimulates the phosphorylation of ribosomal protein S6. Nishimura, J., Deuel, T.F. FEBS Lett. (1983) [Pubmed]
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