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Gene Review

RPS6KB1  -  ribosomal protein S6 kinase, 70kDa,...

Homo sapiens

Synonyms: 70 kDa ribosomal protein S6 kinase 1, P70S6K1, PS6K, Ribosomal protein S6 kinase I, Ribosomal protein S6 kinase beta-1, ...
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Disease relevance of RPS6KB1


Psychiatry related information on RPS6KB1


High impact information on RPS6KB1


Chemical compound and disease context of RPS6KB1


Biological context of RPS6KB1

  • In this review we summarize the structural studies of the amplicon that have been carried out, we outline the evidence implicating the RPS6KB1, TBX2, and PPM1D genes as oncogenes, and we describe some of the other candidate oncogenes from the region [1].
  • The structure defines the hydrophobic pocket termed the "PIF-pocket", which plays a key role in mediating the interaction and phosphorylation of certain substrates such as S6K1 [15].
  • The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor-dependent, and the two phosphorylation events exhibit very different kinetics [16].
  • Herein, we explore the role of the Akt/mTOR/p70S6K pathway in fibronectin-induced NSCLC cell growth [3].
  • The Akt/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K) pathway is considered a central regulator of protein synthesis and of cell proliferation, differentiation, and survival [3].

Anatomical context of RPS6KB1


Associations of RPS6KB1 with chemical compounds


Physical interactions of RPS6KB1

  • Recently, amino acid sufficiency has been demonstrated to selectively regulate p70 S6 kinase (p70(s6k)) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), both of which are targeted by the anti-proliferative drug rapamycin [25].
  • Inhibition of p90 ribosomal S6 kinase-mediated CCAAT/enhancer-binding protein beta activation and cyclooxygenase-2 expression by salicylate [26].
  • Loss of TSC2 GAP activity or disruption of the TSC1/TSC2 complex dysregulates S6K1 activation, which leads to abnormal cell proliferation associated with LAM disease [27].
  • The existence of a PI3-K-dependent signalling complex may enable efficient activation of p70S6K in cells [28].
  • The selective blockade of the p70 S6 kinase activation cascade by the rapamycin-FKBP complex implicates this signalling pathway in the regulation of T cell entry into S phase [29].

Enzymatic interactions of RPS6KB1


Regulatory relationships of RPS6KB1


Other interactions of RPS6KB1


Analytical, diagnostic and therapeutic context of RPS6KB1


  1. The 17q23 amplicon and breast cancer. Sinclair, C.S., Rowley, M., Naderi, A., Couch, F.J. Breast Cancer Res. Treat. (2003) [Pubmed]
  2. AKT activation in human glioblastomas enhances proliferation via TSC2 and S6 kinase signaling. Riemenschneider, M.J., Betensky, R.A., Pasedag, S.M., Louis, D.N. Cancer Res. (2006) [Pubmed]
  3. Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways. Han, S., Khuri, F.R., Roman, J. Cancer Res. (2006) [Pubmed]
  4. Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma. Pene, F., Claessens, Y.E., Muller, O., Viguié, F., Mayeux, P., Dreyfus, F., Lacombe, C., Bouscary, D. Oncogene (2002) [Pubmed]
  5. 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]
  6. Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease. An, W.L., Cowburn, R.F., Li, L., Braak, H., Alafuzoff, I., Iqbal, K., Iqbal, I.G., Winblad, B., Pei, J.J. Am. J. Pathol. (2003) [Pubmed]
  7. Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. Patel, P.H., Tamanoi, F. J. Cell. Sci. (2006) [Pubmed]
  8. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Holz, M.K., Ballif, B.A., Gygi, S.P., Blenis, J. Cell (2005) [Pubmed]
  9. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Kim, D.H., Sarbassov, D.D., Ali, S.M., King, J.E., Latek, R.R., Erdjument-Bromage, H., Tempst, P., Sabatini, D.M. Cell (2002) [Pubmed]
  10. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Hara, K., Maruki, Y., Long, X., Yoshino, K., Oshiro, N., Hidayat, S., Tokunaga, C., Avruch, J., Yonezawa, K. Cell (2002) [Pubmed]
  11. Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors. Koyama, H., Raines, E.W., Bornfeldt, K.E., Roberts, J.M., Ross, R. Cell (1996) [Pubmed]
  12. Muscarinic receptor-mediated activation of p70 S6 kinase 1 (S6K1) in 1321N1 astrocytoma cells: permissive role of phosphoinositide 3-kinase. Tang, X., Wang, L., Proud, C.G., Downes, C.P. Biochem. J. (2003) [Pubmed]
  13. Differential regulation of the p70 S6 kinase pathway by interferon alpha (IFNalpha) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells. Parmar, S., Smith, J., Sassano, A., Uddin, S., Katsoulidis, E., Majchrzak, B., Kambhampati, S., Eklund, E.A., Tallman, M.S., Fish, E.N., Platanias, L.C. Blood (2005) [Pubmed]
  14. Paclitaxel induces inactivation of p70 S6 kinase and phosphorylation of Thr421 and Ser424 via multiple signaling pathways in mitosis. Le, X.F., Hittelman, W.N., Liu, J., McWatters, A., Li, C., Mills, G.B., Bast, R.C. Oncogene (2003) [Pubmed]
  15. High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. Biondi, R.M., Komander, D., Thomas, C.C., Lizcano, J.M., Deak, M., Alessi, D.R., van Aalten, D.M. EMBO J. (2002) [Pubmed]
  16. The mTOR/PI3K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. Shahbazian, D., Roux, P.P., Mieulet, V., Cohen, M.S., Raught, B., Taunton, J., Hershey, J.W., Blenis, J., Pende, M., Sonenberg, N. EMBO J. (2006) [Pubmed]
  17. Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferons. Lekmine, F., Uddin, S., Sassano, A., Parmar, S., Brachmann, S.M., Majchrzak, B., Sonenberg, N., Hay, N., Fish, E.N., Platanias, L.C. J. Biol. Chem. (2003) [Pubmed]
  18. 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]
  19. Mitotic regulation of ribosomal S6 kinase 1 involves Ser/Thr, Pro phosphorylation of consensus and non-consensus sites by Cdc2. Shah, O.J., Ghosh, S., Hunter, T. J. Biol. Chem. (2003) [Pubmed]
  20. Cooperative regulation of p70S6 kinase by receptor tyrosine kinases and G protein-coupled receptors augments airway smooth muscle growth. Billington, C.K., Kong, K.C., Bhattacharyya, R., Wedegaertner, P.B., Panettieri, R.A., Chan, T.O., Penn, R.B. Biochemistry (2005) [Pubmed]
  21. In human endothelial cells amino acids inhibit insulin-induced Akt and ERK1/2 phosphorylation by an mTOR-dependent mechanism. Pellegatta, F., Catapano, A.L., Luzi, L., Terruzzi, I. J. Cardiovasc. Pharmacol. (2006) [Pubmed]
  22. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Roux, P.P., Ballif, B.A., Anjum, R., Gygi, S.P., Blenis, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  23. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins. Xu, Y., Chen, S.Y., Ross, K.N., Balk, S.P. Cancer Res. (2006) [Pubmed]
  24. SKAR is a specific target of S6 kinase 1 in cell growth control. Richardson, C.J., Bröenstrup, M., Fingar, D.C., Jülich, K., Ballif, B.A., Gygi, S., Blenis, J. Curr. Biol. (2004) [Pubmed]
  25. L-Asparaginase inhibits the rapamycin-targeted signaling pathway. Iiboshi, Y., Papst, P.J., Hunger, S.P., Terada, N. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  26. Inhibition of p90 ribosomal S6 kinase-mediated CCAAT/enhancer-binding protein beta activation and cyclooxygenase-2 expression by salicylate. Cieslik, K.A., Zhu, Y., Shtivelband, M., Wu, K.K. J. Biol. Chem. (2005) [Pubmed]
  27. Abnormal Growth of Smooth Muscle-Like Cells in Lymphangioleiomyomatosis: Role for Tumor Suppressor TSC2. Goncharova, E.A., Goncharov, D.A., Spaits, M., Noonan, D.J., Talovskaya, E., Eszterhas, A., Krymskaya, V.P. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  28. p70 S6 kinase is regulated by protein kinase Czeta and participates in a phosphoinositide 3-kinase-regulated signalling complex. Romanelli, A., Martin, K.A., Toker, A., Blenis, J. Mol. Cell. Biol. (1999) [Pubmed]
  29. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Kuo, C.J., Chung, J., Fiorentino, D.F., Flanagan, W.M., Blenis, J., Crabtree, G.R. Nature (1992) [Pubmed]
  30. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro. Alessi, D.R., Kozlowski, M.T., Weng, Q.P., Morrice, N., Avruch, J. Curr. Biol. (1998) [Pubmed]
  31. Receptor association and tyrosine phosphorylation of S6 kinases. Rebholz, H., Panasyuk, G., Fenton, T., Nemazanyy, I., Valovka, T., Flajolet, M., Ronnstrand, L., Stephens, L., West, A., Gout, I.T. FEBS J. (2006) [Pubmed]
  32. Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo. Lizcano, J.M., Deak, M., Morrice, N., Kieloch, A., Hastie, C.J., Dong, L., Schutkowski, M., Reimer, U., Alessi, D.R. J. Biol. Chem. (2002) [Pubmed]
  33. 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]
  34. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. Byfield, M.P., Murray, J.T., Backer, J.M. J. Biol. Chem. (2005) [Pubmed]
  35. Expression of the SNT-1/FRS2 phosphotyrosine binding domain inhibits activation of MAP kinase and PI3-kinase pathways and antiestrogen resistant growth induced by FGF-1 in human breast carcinoma cells. Manuvakhova, M., Thottassery, J.V., Hays, S., Qu, Z., Rentz, S.S., Westbrook, L., Kern, F.G. Oncogene (2006) [Pubmed]
  36. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Garami, A., Zwartkruis, F.J., Nobukuni, T., Joaquin, M., Roccio, M., Stocker, H., Kozma, S.C., Hafen, E., Bos, J.L., Thomas, G. Mol. Cell (2003) [Pubmed]
  37. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Burnett, P.E., Barrow, R.K., Cohen, N.A., Snyder, S.H., Sabatini, D.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  38. Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation. Dufner, A., Andjelkovic, M., Burgering, B.M., Hemmings, B.A., Thomas, G. Mol. Cell. Biol. (1999) [Pubmed]
  39. 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]
  40. S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Djouder, N., Metzler, S.C., Schmidt, A., Wirbelauer, C., Gstaiger, M., Aebersold, R., Hess, D., Krek, W. Mol. Cell (2007) [Pubmed]
  41. 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]
  42. Increased expression of phosphorylated p70S6 kinase and Akt in papillary thyroid cancer tissues. Miyakawa, M., Tsushima, T., Murakami, H., Wakai, K., Isozaki, O., Takano, K. Endocr. J. (2003) [Pubmed]
  43. Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini. Grove, J.R., Banerjee, P., Balasubramanyam, A., Coffer, P.J., Price, D.J., Avruch, J., Woodgett, J.R. Mol. Cell. Biol. (1991) [Pubmed]
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