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P70-S6 Kinase 1: Wikis


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Ribosomal protein S6 kinase, 70kDa, polypeptide 1
Symbols RPS6KB1; PS6K; S6K; S6K1; STK14A; p70(S6K)-alpha; p70-S6K; p70-alpha
External IDs OMIM608938 HomoloGene81703 GeneCards: RPS6KB1 Gene
RNA expression pattern
PBB GE RPS6KB1 204171 at tn.png
PBB GE RPS6KB1 211578 s at tn.png
More reference expression data
Species Human Mouse
Entrez 6198 n/a
Ensembl ENSG00000108443 n/a
UniProt P23443 n/a
RefSeq (mRNA) NM_003161 n/a
RefSeq (protein) NP_003152 n/a
Location (UCSC) Chr 17:
55.33 - 55.38 Mb
PubMed search [1] n/a

Ribosomal protein S6 kinase beta-1 is an enzyme that in humans is encoded by the RPS6KB1 gene.[1][2]

This gene encodes a member of the RSK (ribosomal s6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates several residues of the S6 ribosomal protein. The kinase activity of this protein leads to an increase in protein synthesis and cell proliferation. Amplification of the region of DNA encoding this gene and overexpression of this kinase are seen in some breast cancer cell lines. Alternate translational start sites have been described and alternate transcriptional splice variants have been observed but have not been thoroughly characterized.[2]



P70-S6 Kinase 1 has been shown to interact with CSNK2B,[3] EIF3B,[4] COASY,[5] KIAA1303,[6][7][8][9] POLDIP3,[10] Mammalian target of rapamycin,[6][8][11][9][12][13][14][15][16][17][18][19][20][21][22] PPP2R2A,[23][24] RBX1[25] and Ubiquitin C.[25]


  1. ^ Grove JR, Banerjee P, Balasubramanyam A, Coffer PJ, Price DJ, Avruch J, Woodgett JR (Nov 1991). "Cloning and expression of two human p70 S6 kinase polypeptides differing only at their amino termini". Mol Cell Biol 11 (11): 5541–50. PMID 1922062.  
  2. ^ a b "Entrez Gene: RPS6KB1 ribosomal protein S6 kinase, 70kDa, polypeptide 1".  
  3. ^ Panasyuk, Ganna; Nemazanyy Ivan, Zhyvoloup Alexander, Bretner Maria, Litchfield David W, Filonenko Valeriy, Gout Ivan T (Oct. 2006). "Nuclear export of S6K1 II is regulated by protein kinase CK2 phosphorylation at Ser-17". J. Biol. Chem. (United States) 281 (42): 31188–201. doi:10.1074/jbc.M602618200. ISSN 0021-9258. PMID 16895915.  
  4. ^ Holz, Marina K; Ballif Bryan A, Gygi Steven P, Blenis John (Nov. 2005). "mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events". Cell (United States) 123 (4): 569–80. doi:10.1016/j.cell.2005.10.024. ISSN 0092-8674. PMID 16286006.  
  5. ^ Nemazanyy, Ivan; Panasyuk Ganna, Zhyvoloup Alexander, Panayotou George, Gout Ivan T, Filonenko Valeriy (Dec. 2004). "Specific interaction between S6K1 and CoA synthase: a potential link between the mTOR/S6K pathway, CoA biosynthesis and energy metabolism". FEBS Lett. (Netherlands) 578 (3): 357–62. doi:10.1016/j.febslet.2004.10.091. ISSN 0014-5793. PMID 15589845.  
  6. ^ a b Ali, Siraj M; Sabatini David M (May. 2005). "Structure of S6 kinase 1 determines whether raptor-mTOR or rictor-mTOR phosphorylates its hydrophobic motif site". J. Biol. Chem. (United States) 280 (20): 19445–8. doi:10.1074/jbc.C500125200. ISSN 0021-9258. PMID 15809305.  
  7. ^ Ha, Sang Hoon; Kim Do-Hyung, Kim Il-Shin, Kim Jung Hwan, Lee Mi Nam, Lee Hyun Ju, Kim Jong Heon, Jang Sung Key, Suh Pann-Ghill, Ryu Sung Ho (Dec. 2006). "PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals". Cell. Signal. (England) 18 (12): 2283–91. doi:10.1016/j.cellsig.2006.05.021. ISSN 0898-6568. PMID 16837165.  
  8. ^ a b Hara, Kenta; Maruki Yoshiko, Long Xiaomeng, Yoshino Ken-ichi, Oshiro Noriko, Hidayat Sujuti, Tokunaga Chiharu, Avruch Joseph, Yonezawa Kazuyoshi (Jul. 2002). "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action". Cell (United States) 110 (2): 177–89. ISSN 0092-8674. PMID 12150926.  
  9. ^ a b Nojima, Hiroki; Tokunaga Chiharu, Eguchi Satoshi, Oshiro Noriko, Hidayat Sujuti, Yoshino Ken-ichi, Hara Kenta, Tanaka Noriaki, Avruch Joseph, Yonezawa Kazuyoshi (May. 2003). "The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif". J. Biol. Chem. (United States) 278 (18): 15461–4. doi:10.1074/jbc.C200665200. ISSN 0021-9258. PMID 12604610.  
  10. ^ Richardson, Celeste J; Bröenstrup Mark, Fingar Diane C, Jülich Kristina, Ballif Bryan A, Gygi Steven, Blenis John (Sep. 2004). "SKAR is a specific target of S6 kinase 1 in cell growth control". Curr. Biol. (England) 14 (17): 1540–9. doi:10.1016/j.cub.2004.08.061. ISSN 0960-9822. PMID 15341740.  
  11. ^ Chiang, Gary G; Abraham Robert T (Jul. 2005). "Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase". J. Biol. Chem. (United States) 280 (27): 25485–90. doi:10.1074/jbc.M501707200. ISSN 0021-9258. PMID 15899889.  
  12. ^ Holz, Marina K; Blenis John (Jul. 2005). "Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase". J. Biol. Chem. (United States) 280 (28): 26089–93. doi:10.1074/jbc.M504045200. ISSN 0021-9258. PMID 15905173.  
  13. ^ Isotani, S; Hara K, Tokunaga C, Inoue H, Avruch J, Yonezawa K (Nov. 1999). "Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro". J. Biol. Chem. (UNITED STATES) 274 (48): 34493–8. ISSN 0021-9258. PMID 10567431.  
  14. ^ Long, Xiaomeng; Lin Yenshou, Ortiz-Vega Sara, Yonezawa Kazuyoshi, Avruch Joseph (Apr. 2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. (England) 15 (8): 702–13. doi:10.1016/j.cub.2005.02.053. ISSN 0960-9822. PMID 15854902.  
  15. ^ Toral-Barza, Lourdes; Zhang Wei-Guo, Lamison Craig, Larocque James, Gibbons James, Yu Ker (Jun. 2005). "Characterization of the cloned full-length and a truncated human target of rapamycin: activity, specificity, and enzyme inhibition as studied by a high capacity assay". Biochem. Biophys. Res. Commun. (United States) 332 (1): 304–10. doi:10.1016/j.bbrc.2005.04.117. ISSN 0006-291X. PMID 15896331.  
  16. ^ Saitoh, Masao; Pullen Nicholas, Brennan Paul, Cantrell Doreen, Dennis Patrick B, Thomas George (May. 2002). "Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site". J. Biol. Chem. (United States) 277 (22): 20104–12. doi:10.1074/jbc.M201745200. ISSN 0021-9258. PMID 11914378.  
  17. ^ Kim, Do-Hyung; Sarbassov D D, Ali Siraj M, King Jessie E, Latek Robert R, Erdjument-Bromage Hediye, Tempst Paul, Sabatini David M (Jul. 2002). "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery". Cell (United States) 110 (2): 163–75. ISSN 0092-8674. PMID 12150925.  
  18. ^ Edinger, Aimee L; Linardic Corinne M, Chiang Gary G, Thompson Craig B, Abraham Robert T (Dec. 2003). "Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells". Cancer Res. (United States) 63 (23): 8451–60. ISSN 0008-5472. PMID 14679009.  
  19. ^ Leone, Marilisa; Crowell Kevin J, Chen Jinhua, Jung Dawoon, Chiang Gary G, Sareth Sina, Abraham Robert T, Pellecchia Maurizio (Aug. 2006). "The FRB domain of mTOR: NMR solution structure and inhibitor design". Biochemistry (United States) 45 (34): 10294–302. doi:10.1021/bi060976+. ISSN 0006-2960. PMID 16922504.  
  20. ^ Takahashi, T; Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K (Sep. 2000). "Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro". Genes Cells (ENGLAND) 5 (9): 765–75. ISSN 1356-9597. PMID 10971657.  
  21. ^ Burnett, P E; Barrow R K, Cohen N A, Snyder S H, Sabatini D M (Feb. 1998). "RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (4): 1432–7. ISSN 0027-8424. PMID 9465032.  
  22. ^ Sarbassov, Dos D; Sabatini David M (Nov. 2005). "Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex". J. Biol. Chem. (United States) 280 (47): 39505–9. doi:10.1074/jbc.M506096200. ISSN 0021-9258. PMID 16183647.  
  23. ^ Peterson, R T; Desai B N, Hardwick J S, Schreiber S L (Apr. 1999). "Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 96 (8): 4438–42. ISSN 0027-8424. PMID 10200280.  
  24. ^ Bishop, Jessica D; Nien Wei Lun, Dauphinee Shauna M, Too Catherine K L (Aug. 2006). "Prolactin activates mammalian target-of-rapamycin through phosphatidylinositol 3-kinase and stimulates phosphorylation of p70S6K and 4E-binding protein-1 in lymphoma cells". J. Endocrinol. (England) 190 (2): 307–12. doi:10.1677/joe.1.06368. ISSN 0022-0795. PMID 16899564.  
  25. ^ a b Panasyuk, Ganna; Nemazanyy Ivan, Filonenko Valeriy, Gout Ivan (May. 2008). "Ribosomal protein S6 kinase 1 interacts with and is ubiquitinated by ubiquitin ligase ROC1". Biochem. Biophys. Res. Commun. (United States) 369 (2): 339–43. doi:10.1016/j.bbrc.2008.02.016. PMID 18279656.  

Further reading

  • Proud CG (1997). "p70 S6 kinase: an enigma with variations.". Trends Biochem. Sci. 21 (5): 181–5. PMID 8871403.  
  • Manning BD (2004). "Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis.". J. Cell Biol. 167 (3): 399–403. doi:10.1083/jcb.200408161. PMID 15533996.  
  • Moser BA, Dennis PB, Pullen N, et al. (1997). "Dual requirement for a newly identified phosphorylation site in p70s6k.". Mol. Cell. Biol. 17 (9): 5648–55. PMID 9271440.  
  • Alessi DR, Kozlowski MT, Weng QP, et al. (1998). "3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro.". Curr. Biol. 8 (2): 69–81. doi:10.1016/S0960-9822(98)70037-5. PMID 9427642.  
  • Pullen N, Dennis PB, Andjelkovic M, et al. (1998). "Phosphorylation and activation of p70s6k by PDK1.". Science 279 (5351): 707–10. doi:10.1126/science.279.5351.707. PMID 9445476.  
  • Burnett PE, Blackshaw S, Lai MM, et al. (1998). "Neurabin is a synaptic protein linking p70 S6 kinase and the neuronal cytoskeleton.". Proc. Natl. Acad. Sci. U.S.A. 95 (14): 8351–6. doi:10.1073/pnas.95.14.8351. PMID 9653190.  
  • Gout I, Minami T, Hara K, et al. (1998). "Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase beta containing a proline-rich region.". J. Biol. Chem. 273 (46): 30061–4. doi:10.1074/jbc.273.46.30061. PMID 9804755.  
  • Barcova M, Speth C, Kacani L, et al. (1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 envelope protein of human immunodeficiency virus type 1.". Pflugers Arch. 437 (4): 538–46. doi:10.1007/s004240050815. PMID 10089566.  
  • Couch FJ, Wang XY, Wu GJ, et al. (1999). "Localization of PS6K to chromosomal region 17q23 and determination of its amplification in breast cancer.". Cancer Res. 59 (7): 1408–11. PMID 10197603.  
  • Balendran A, Currie R, Armstrong CG, et al. (2000). "Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 S6 kinase in vivo at Thr-412 as well as Thr-252.". J. Biol. Chem. 274 (52): 37400–6. doi:10.1074/jbc.274.52.37400. PMID 10601311.  
  • Speth C, Joebstl B, Barcova M, Dierich MP (2000). "HIV-1 envelope protein gp41 modulates expression of interleukin-10 and chemokine receptors on monocytes, astrocytes and neurones.". AIDS 14 (6): 629–36. doi:10.1097/00002030-200004140-00001. PMID 10807185.  
  • Wilson KF, Wu WJ, Cerione RA (2001). "Cdc42 stimulates RNA splicing via the S6 kinase and a novel S6 kinase target, the nuclear cap-binding complex.". J. Biol. Chem. 275 (48): 37307–10. doi:10.1074/jbc.C000482200. PMID 10973943.  
  • Armstrong JL, Bonavaud SM, Toole BJ, Yeaman SJ (2001). "Regulation of glycogen synthesis by amino acids in cultured human muscle cells.". J. Biol. Chem. 276 (2): 952–6. doi:10.1074/jbc.M004812200. PMID 11013237.  
  • Diggle TA, Subkhankulova T, Lilley KS, et al. (2001). "Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity.". Biochem. J. 353 (Pt 3): 621–6. doi:10.1042/0264-6021:3530621. PMID 11171059.  
  • Sapkota GP, Kieloch A, Lizcano JM, et al. (2001). "Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth.". J. Biol. Chem. 276 (22): 19469–82. doi:10.1074/jbc.M009953200. PMID 11297520.  
  • Remy I, Michnick SW (2001). "Visualization of biochemical networks in living cells.". Proc. Natl. Acad. Sci. U.S.A. 98 (14): 7678–83. doi:10.1073/pnas.131216098. PMID 11438723.  
  • Wang X, Li W, Williams M, et al. (2001). "Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase.". EMBO J. 20 (16): 4370–9. doi:10.1093/emboj/20.16.4370. PMID 11500364.  
  • Belham C, Comb MJ, Avruch J (2001). "Identification of the NIMA family kinases NEK6/7 as regulators of the p70 ribosomal S6 kinase.". Curr. Biol. 11 (15): 1155–67. doi:10.1016/S0960-9822(01)00369-4. PMID 11516946.  

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