Gene Symbol: Rps6kb1
Description: ribosomal protein S6 kinase, polypeptide 1
Alias: 2610318I15Rik, 4732464A07Rik, 70kDa, AA959758, AI256796, AI314060, P70S6K1, S6K, S6K1, p70/85s6k, p70s6k, ribosomal protein S6 kinase beta-1, 70 kDa ribosomal protein S6 kinase 1, S6K-beta-1, p70 S6 kinase alpha, p70 S6K-alpha, p70 S6KA, p70 ribosomal S6 kinase alpha, p70-S6K 1, ribosomal protein S6 kinase I, ribosomal protein S6 kinase, 70kD, polypeptide 1
Species: mouse
Products:     Rps6kb1

Top Publications

  1. Zhang J, Gao Z, Yin J, Quon M, Ye J. S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. J Biol Chem. 2008;283:35375-82 pubmed publisher
    S6K1 (p70S6K) is a serine kinase downstream from Akt in the insulin signaling pathway that is involved in negative feedback regulation of insulin action. S6K1 is also activated by TNF-alpha, a pro-inflammatory cytokine...
  2. Hentges K, Sirry B, Gingeras A, Sarbassov D, Sonenberg N, Sabatini D, et al. FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc Natl Acad Sci U S A. 2001;98:13796-801 pubmed
    ..kinase activity and mediates the cellular response to mitogens through signaling to p70s6 kinase (p70(s6k)) and 4E-BP1, resulting in an increase in translation of subsets of cellular mRNAs...
  3. Cota D, Matter E, Woods S, Seeley R. The role of hypothalamic mammalian target of rapamycin complex 1 signaling in diet-induced obesity. J Neurosci. 2008;28:7202-8 pubmed publisher
    ..mTORC1 signaling in the HF group, whereas it significantly induced phosphorylation of both S6 kinase 1 (S6K1) and S6 ribosomal protein (S6) in the LF group...
  4. Ohanna M, Sobering A, Lapointe T, Lorenzo L, Praud C, Petroulakis E, et al. Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol. 2005;7:286-94 pubmed
    ..Here we show that S6 kinase 1 (S6K1), a protein kinase activated by nutrients and insulin-like growth factors (IGFs), is essential for the control of ..
  5. Harrington L, Findlay G, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004;166:213-23 pubmed
    ..The tuberous sclerosis complex (TSC1-2) suppresses cell growth by negatively regulating a protein kinase, p70S6K (S6K1), which generally requires PI3K signals for its activation...
  6. Otulakowski G, Duan W, Gandhi S, O Brodovich H. Steroid and oxygen effects on eIF4F complex, mTOR, and ENaC translation in fetal lung epithelia. Am J Respir Cell Mol Biol. 2007;37:457-66 pubmed
    ..We speculate that at birth increased Po(2) acts with GC through an mTOR-related pathway to increase alpha-ENaC protein synthesis, thereby promoting lung fluid absorption. ..
  7. Carnevalli L, Masuda K, Frigerio F, Le Bacquer O, Um S, Gandin V, et al. S6K1 plays a critical role in early adipocyte differentiation. Dev Cell. 2010;18:763-74 pubmed publisher
    Earlier, we reported that S6K1(-/-) mice have reduced body fat mass, have elevated rates of lipolysis, have severely decreased adipocyte size, and are resistant to high fat diet (HFD)-induced obesity...
  8. Narayanan U, Nalavadi V, Nakamoto M, Thomas G, Ceman S, Bassell G, et al. S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade. J Biol Chem. 2008;283:18478-82 pubmed publisher
    ..Here we identify ribosomal protein S6 kinase (S6K1) as a major FMRP kinase in the mouse hippocampus, finding that activity-dependent phosphorylation of FMRP by S6K1 ..
  9. Park I, Erbay E, Nuzzi P, Chen J. Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1. Exp Cell Res. 2005;309:211-9 pubmed
    ..rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors...

More Information


  1. Pende M, Kozma S, Jaquet M, Oorschot V, Burcelin R, Le Marchand Brustel Y, et al. Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature. 2000;408:994-7 pubmed
    ..The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance. ..
  2. Harada H, Andersen J, Mann M, Terada N, Korsmeyer S. p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD. Proc Natl Acad Sci U S A. 2001;98:9666-70 pubmed
    ..The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components...
  3. Um S, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004;431:200-5 pubmed
    ..Recently, mice deficient for S6 Kinase 1 (S6K1), an effector of the mammalian target of rapamycin (mTOR) that acts to integrate nutrient and insulin signals, were ..
  4. Gutierrez Uzquiza A, Arechederra M, Bragado P, Aguirre Ghiso J, Porras A. p38? mediates cell survival in response to oxidative stress via induction of antioxidant genes: effect on the p70S6K pathway. J Biol Chem. 2012;287:2632-42 pubmed publisher
    ..that this p38?-dependent antioxidant response allows WT cells to maintain an efficient activation of the mTOR/p70S6K pathway...
  5. Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma S. Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J. 1998;17:6649-59 pubmed
    Recent studies have shown that the p70(s6k)/p85(s6k) signaling pathway plays a critical role in cell growth by modulating the translation of a family of mRNAs termed 5'TOPs, which encode components of the protein synthetic apparatus...
  6. Selman C, Tullet J, Wieser D, Irvine E, Lingard S, Choudhury A, et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009;326:140-4 pubmed publisher
    ..We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased ..
  7. Dagon Y, HUR E, Zheng B, Wellenstein K, Cantley L, Kahn B. p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake. Cell Metab. 2012;16:104-12 pubmed publisher
    ..This discovery has broad biologic implications since mTOR-p70S6 kinase and AMPK have multiple, fundamental and generally opposing cellular effects that regulate metabolism, cell growth, and development. ..
  8. Yepuri G, Velagapudi S, Xiong Y, Rajapakse A, Montani J, Ming X, et al. Positive crosstalk between arginase-II and S6K1 in vascular endothelial inflammation and aging. Aging Cell. 2012;11:1005-16 pubmed publisher
    Augmented activities of both arginase and S6K1 are involved in endothelial dysfunction in aging...
  9. Pende M, Um S, Mieulet V, Sticker M, Goss V, Mestan J, et al. S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5'-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. Mol Cell Biol. 2004;24:3112-24 pubmed
    ..In mammals, two genes encoding homologous S6Ks, S6K1 and S6K2, have been identified...
  10. Lai K, Leong W, Chau J, Jia D, Zeng L, Liu H, et al. S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response. EMBO J. 2010;29:2994-3006 pubmed publisher
    ..By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, we identified S6K1 as a multifaceted regulator of Mdm2. DNA damage activates mTOR-S6K1 through p38alpha MAPK...
  11. Xia T, Cheng Y, Zhang Q, Xiao F, Liu B, Chen S, et al. S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid. Diabetes. 2012;61:2461-71 pubmed
    ..intracerebroventricular injection of adenoviral vectors to identify a novel role for hypothalamic p70 S6 kinase 1 (S6K1), a major downstream effector of the kinase mammalian target of rapamycin, in leucine deprivation stimulation of ..
  12. Aguilar V, Alliouachene S, Sotiropoulos A, Sobering A, Athea Y, Djouadi F, et al. S6 kinase deletion suppresses muscle growth adaptations to nutrient availability by activating AMP kinase. Cell Metab. 2007;5:476-87 pubmed
    ..Energy stress and muscle cell atrophy are specifically triggered by the S6K1 deletion, independent of S6K2 activity...
  13. Hornberger T, Sukhija K, Wang X, Chien S. mTOR is the rapamycin-sensitive kinase that confers mechanically-induced phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k). FEBS Lett. 2007;581:4562-6 pubmed
    Mechanical stretch induces phosphorylation of the hydrophobic motif site Thr(389) in p70(S6k) through a rapamycin-sensitive (RS) pathway that involves a unique PI3K-independent mechanism...
  14. Veilleux A, Houde V, Bellmann K, Marette A. Chronic inhibition of the mTORC1/S6K1 pathway increases insulin-induced PI3K activity but inhibits Akt2 and glucose transport stimulation in 3T3-L1 adipocytes. Mol Endocrinol. 2010;24:766-78 pubmed publisher
    ..Acute inhibition of mTORC1/S6K1 by rapamycin increases insulin signaling and glucose uptake in myocytes and adipocytes, but whether these effects ..
  15. Arif A, Terenzi F, Potdar A, Jia J, Sacks J, China A, et al. EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice. Nature. 2017;542:357-361 pubmed publisher
    ..ageing are activated by the mammalian target of rapamycin complex 1 (mTORC1) and p70 ribosomal protein S6 kinase 1 (S6K1) axis...
  16. Chakravarthy M, Zhu Y, Wice M, Coleman T, Pappan K, Marshall C, et al. Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age. Diabetes. 2008;57:2698-707 pubmed publisher
  17. Crowell K, Steiner J, Coleman C, Lang C. Decreased Whole-Body Fat Mass Produced by Chronic Alcohol Consumption is Associated with Activation of S6K1-Mediated Protein Synthesis and Increased Autophagy in Epididymal White Adipose Tissue. Alcohol Clin Exp Res. 2016;40:1832-45 pubmed publisher
    ..Instead, a selective increase in phosphorylation of S6K1 and its downstream substrates, S6 and eIF4B was detected in alcohol-fed mice...
  18. Tan Y, You H, Wu C, Altomare D, Testa J. Appl1 is dispensable for mouse development, and loss of Appl1 has growth factor-selective effects on Akt signaling in murine embryonic fibroblasts. J Biol Chem. 2010;285:6377-89 pubmed publisher
    ..Our studies suggest that Appl1 is dispensable for development and only participate in Akt signaling under certain conditions. ..
  19. Zito C, Qin H, Blenis J, Bennett A. SHP-2 regulates cell growth by controlling the mTOR/S6 kinase 1 pathway. J Biol Chem. 2007;282:6946-53 pubmed
    ..S 6 ribosomal kinase 1 (S6K1), which is activated by the mammalian target of rapamycin, is critical for cell growth...
  20. Goc A, Sabbineni H, Abdalla M, Somanath P. p70 S6-kinase mediates the cooperation between Akt1 and Mek1 pathways in fibroblast-mediated extracellular matrix remodeling. Biochim Biophys Acta. 2015;1853:1626-35 pubmed publisher
    ..Furthermore, Akt1 and Mek1 cooperated in mediating ECM assembly via activation of integrin β1. Together, we show for the first time that Akt1 and Mek1 pathways cooperate in the regulation of ECM remodeling by the fibroblasts. ..
  21. Hasumi Y, Baba M, Ajima R, Hasumi H, Valera V, Klein M, et al. Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci U S A. 2009;106:18722-7 pubmed publisher
  22. Kenerson H, Subramanian S, McIntyre R, Kazami M, Yeung R. Livers with constitutive mTORC1 activity resist steatosis independent of feedback suppression of Akt. PLoS ONE. 2015;10:e0117000 pubmed publisher
    ..the in vivo mechanism of steatosis-resistance secondary to mTORC1 activation, with emphasis on the role of S6K1-mediated feedback inhibition of AKT...
  23. McMullen J, Shioi T, Zhang L, Tarnavski O, Sherwood M, Dorfman A, et al. Deletion of ribosomal S6 kinases does not attenuate pathological, physiological, or insulin-like growth factor 1 receptor-phosphoinositide 3-kinase-induced cardiac hypertrophy. Mol Cell Biol. 2004;24:6231-40 pubmed
    ..For this purpose, we generated and characterized cardiac-specific S6K1 and S6K2 transgenic mice and subjected S6K1(-/-), S6K2(-/-), and S6K1(-/-) S6K2(-/-) mice to a pathological stress (..
  24. Nakagawa T, Araki T, Nakagawa M, Hirao A, Unno M, Nakayama K. S6 Kinase- and β-TrCP2-Dependent Degradation of p19Arf Is Required for Cell Proliferation. Mol Cell Biol. 2015;35:3517-27 pubmed publisher
    ..Whereas mTOR activates translation through ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4E-BP), how it facilitates cell proliferation has ..
  25. Antion M, Hou L, Wong H, Hoeffer C, Klann E. mGluR-dependent long-term depression is associated with increased phosphorylation of S6 and synthesis of elongation factor 1A but remains expressed in S6K-deficient mice. Mol Cell Biol. 2008;28:2996-3007 pubmed publisher
    ..We found that mGluR-LTD was associated with increased phosphorylation of p70S6 kinase (S6K1) and S6, as well as the synthesis of the 5'TOP-encoded protein elongation factor 1A (EF1A)...
  26. Kroczynska B, Sharma B, Eklund E, Fish E, Platanias L. Regulatory effects of programmed cell death 4 (PDCD4) protein in interferon (IFN)-stimulated gene expression and generation of type I IFN responses. Mol Cell Biol. 2012;32:2809-22 pubmed publisher
    ..This IFN-?-dependent phosphorylation is mediated by either the p70 S6 kinase (S6K) or the p90 ribosomal protein S6K (RSK) in a cell-type-specific manner...
  27. Treins C, Alliouachene S, Hassouna R, Xie Y, Birnbaum M, Pende M. The combined deletion of S6K1 and Akt2 deteriorates glycemic control in a high-fat diet. Mol Cell Biol. 2012;32:4001-11 pubmed publisher
    ..Mice lacking the mTORC1 substrate S6 kinase 1 (S6K1) maintain proper glycemic control with a high-fat diet...
  28. Foerster P, Daclin M, Asm S, Faucourt M, Boletta A, Genovesio A, et al. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development. 2017;144:201-210 pubmed publisher
    ..These results suggest that primary cilia regulate ventricle morphogenesis by acting as a brake on the mTORC1 pathway. This opens new avenues for the diagnosis and treatment of hydrocephalus. ..
  29. Valjent E, Bertran Gonzalez J, Bowling H, Lopez S, Santini E, Matamales M, et al. Haloperidol regulates the state of phosphorylation of ribosomal protein S6 via activation of PKA and phosphorylation of DARPP-32. Neuropsychopharmacology. 2011;36:2561-70 pubmed publisher
    ..These results identify PKA as a major rpS6 kinase in neuronal cells and suggest that regulation of protein synthesis through rpS6 may be a potential target of antipsychotic drugs. ..
  30. Dodd K, Yang J, Shen M, Sampson J, Tee A. mTORC1 drives HIF-1? and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3. Oncogene. 2015;34:2239-50 pubmed publisher
    ..co-operative regulation of both initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase-1 (S6K1), whereas HIF-1? degradation remains unaffected...
  31. Feng Q, Di R, Tao F, Chang Z, Lu S, Fan W, et al. PDK1 regulates vascular remodeling and promotes epithelial-mesenchymal transition in cardiac development. Mol Cell Biol. 2010;30:3711-21 pubmed publisher
    ..Taken together, these results have revealed an essential role of PDK1 in cardiovascular development through activation of Akt and Snail. ..
  32. De Miguel M, Cheng L, Holland E, Federspiel M, Donovan P. Dissection of the c-Kit signaling pathway in mouse primordial germ cells by retroviral-mediated gene transfer. Proc Natl Acad Sci U S A. 2002;99:10458-63 pubmed
    ..Such technology for manipulating gene expression in PGCs will allow many of the molecular mechanisms regulating germ cell growth, behavior, and differentiation to be comprehensively analyzed. ..
  33. Tsutsumi N, Yonemitsu Y, Shikada Y, Onimaru M, Tanii M, Okano S, et al. Essential role of PDGFRalpha-p70S6K signaling in mesenchymal cells during therapeutic and tumor angiogenesis in vivo: role of PDGFRalpha during angiogenesis. Circ Res. 2004;94:1186-94 pubmed
    ..In this study, we propose that the platelet-derived growth factor receptor-alpha (PDGFRalpha)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by ..
  34. Barilari M, Bonfils G, Treins C, Koka V, De Villeneuve D, Fabrega S, et al. ZRF1 is a novel S6 kinase substrate that drives the senescence programme. EMBO J. 2017;36:736-750 pubmed publisher
    ..Our findings reveal a mechanism by which nutrient sensing pathways impact on cell senescence through the activation of mTORC1-S6 kinases and the phosphorylation of ZRF1. ..
  35. Bermudez Silva F, Romero Zerbo S, Haissaguerre M, Ruz Maldonado I, Lhamyani S, El Bekay R, et al. The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice. Dis Model Mech. 2016;9:51-61 pubmed publisher
    ..analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance ..
  36. Espeillac C, Mitchell C, Celton Morizur S, Chauvin C, Koka V, Gillet C, et al. S6 kinase 1 is required for rapamycin-sensitive liver proliferation after mouse hepatectomy. J Clin Invest. 2011;121:2821-32 pubmed publisher
    ..In addition, genetic deletion of S6 kinase 1 (S6K1) caused a delay in S phase entry in hepatocytes after hepatectomy...
  37. Um S, Sticker Jantscheff M, Chau G, Vintersten K, Mueller M, Gangloff Y, et al. S6K1 controls pancreatic ? cell size independently of intrauterine growth restriction. J Clin Invest. 2015;125:2736-47 pubmed publisher
    ..As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving ..
  38. Bae E, Xu J, Oh D, Bandyopadhyay G, Lagakos W, Keshwani M, et al. Liver-specific p70 S6 kinase depletion protects against hepatic steatosis and systemic insulin resistance. J Biol Chem. 2012;287:18769-80 pubmed publisher
    ..We created a mouse model of liver-specific knockdown of p70 S6 kinase (S6K) (L-S6K-KD) by systemic delivery of an adeno-associated virus carrying a shRNA for S6K and examined the effects on ..
  39. Kim H, Park E, Oh M, Park S, Shin K, Choi S, et al. Central administration of metformin into the third ventricle of C57BL/6 mice decreases meal size and number and activates hypothalamic S6 kinase. Am J Physiol Regul Integr Comp Physiol. 2013;305:R499-505 pubmed publisher
    ..key hypothalamic energy sensors, including adenosine monophosphate-activated protein kinase (AMPK) and S6 kinase (S6K)...
  40. Parker W, Orlova K, Parker W, Birnbaum J, Krymskaya V, Goncharov D, et al. Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder. Sci Transl Med. 2013;5:182ra53 pubmed publisher
    ..depletion is prevented by mTORC1 inhibition with rapamycin or inhibition of its downstream effector p70 S6 kinase (p70S6K) with the drug PF-4708671 (p70S6Ki)...
  41. Varea O, Escoll M, Diez H, Garrido J, Wandosell F. Oestradiol signalling through the Akt-mTORC1-S6K1. Biochim Biophys Acta. 2013;1833:1052-64 pubmed publisher
    ..All these data demonstrate a new mechanism regulated by oestradiol, at least in neuronal morphogenesis. ..
  42. Bhattacharya A, Kaphzan H, Alvarez Dieppa A, Murphy J, Pierre P, Klann E. Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. Neuron. 2012;76:325-37 pubmed publisher
    ..We sought to perturb p70 ribosomal S6 kinase 1 (S6K1), a key translation initiation and elongation regulator, in FXS model mice...
  43. Pereira A, Clemente C, Cardoso A, Theizen T, Rocco S, Judice C, et al. MEF2C silencing attenuates load-induced left ventricular hypertrophy by modulating mTOR/S6K pathway in mice. PLoS ONE. 2009;4:e8472 pubmed publisher
    ..Additionally, MEF2C depletion was accompanied by defective activation of S6K in response to pressure overload...
  44. Hu S, Katz M, Chin S, Qi X, Cruz J, Ibebunjo C, et al. MNK2 inhibits eIF4G activation through a pathway involving serine-arginine-rich protein kinase in skeletal muscle. Sci Signal. 2012;5:ra14 pubmed publisher
    ..we found that MNK2 interacted with mTOR and inhibited phosphorylation of the mTOR target, the ribosomal kinase p70S6K (70-kD ribosomal protein S6 kinase), through a mechanism independent of the kinase activity of MNK2...
  45. Ka M, Condorelli G, Woodgett J, Kim W. mTOR regulates brain morphogenesis by mediating GSK3 signaling. Development. 2014;141:4076-86 pubmed publisher
    ..Our findings reveal that the interaction between mTOR and GSK3 signaling plays an essential role in dynamic homeostasis of neural progenitors during brain development. ..
  46. Scott C, Walker D, Cwiklinski E, Tait C, Tee A, Land S. Control of HIF-1{alpha} and vascular signaling in fetal lung involves cross talk between mTORC1 and the FGF-10/FGFR2b/Spry2 airway branching periodicity clock. Am J Physiol Lung Cell Mol Physiol. 2010;299:L455-71 pubmed publisher
    ..Thus, mTORC1 links HIF-1?-driven vasculogenesis with the FGF-10/FGFR2b/Spry2 airway branching periodicity regulator. ..
  47. Pastor M, García Yébenes I, Fradejas N, Pérez Ortiz J, Mora Lee S, Tranque P, et al. mTOR/S6 kinase pathway contributes to astrocyte survival during ischemia. J Biol Chem. 2009;284:22067-78 pubmed publisher
    ..We detected a robust down-regulation of S6 kinase 1 (S6K1) mRNA that was accompanied by a sharp decrease in protein levels and activity...
  48. Cheatham L, Monfar M, Chou M, Blenis J. Structural and functional analysis of pp70S6k. Proc Natl Acad Sci U S A. 1995;92:11696-700 pubmed
    ..Our results indicate that both the N and C termini participate in the complex regulation of pp70S6k activity. ..
  49. Sinclair C, Bommakanti G, Gardinassi L, Loebbermann J, Johnson M, Hakimpour P, et al. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation. Science. 2017;357:1014-1021 pubmed publisher
    ..mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. ..
  50. Challen G, Gardiner B, Caruana G, Kostoulias X, Martinez G, Crowe M, et al. Temporal and spatial transcriptional programs in murine kidney development. Physiol Genomics. 2005;23:159-71 pubmed
  51. Winbanks C, Weeks K, Thomson R, Sepulveda P, Beyer C, Qian H, et al. Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin. J Cell Biol. 2012;197:997-1008 pubmed publisher
    ..These effects were attenuated by inhibition of mTOR or deletion of S6K1/2...
  52. Vijayaraj P, Kröger C, Reuter U, Windoffer R, Leube R, Magin T. Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor. J Cell Biol. 2009;187:175-84 pubmed publisher
    ..Our findings demonstrate a novel keratin function upstream of mTOR signaling via GLUT localization and have implications for pathomechanisms and therapy approaches for keratin disorders and the analysis of other gene families. ..
  53. Caccamo A, Branca C, Talboom J, Shaw D, Turner D, Ma L, et al. Reducing Ribosomal Protein S6 Kinase 1 Expression Improves Spatial Memory and Synaptic Plasticity in a Mouse Model of Alzheimer's Disease. J Neurosci. 2015;35:14042-56 pubmed publisher
    ..Suppression of the ribosomal protein S6 kinase 1 (S6K1) increases healthspan and lifespan in several organisms, from nematodes to mammals...
  54. Uno K, Yamada T, Ishigaki Y, Imai J, Hasegawa Y, Sawada S, et al. A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals. Nat Commun. 2015;6:7940 pubmed publisher
    ..AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver...
  55. Alliouachene S, Tuttle R, Boumard S, Lapointe T, Berissi S, Germain S, et al. Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation. J Clin Invest. 2008;118:3629-38 pubmed publisher
    ..To address the role of the mammalian target of rapamycin (mTOR) substrate S6K1 in the MyrAkt1-mediated phenotype, we crossed RIP-MyrAkt1 and S6K1-deficient mice...
  56. Proulx K, Cota D, Woods S, Seeley R. Fatty acid synthase inhibitors modulate energy balance via mammalian target of rapamycin complex 1 signaling in the central nervous system. Diabetes. 2008;57:3231-8 pubmed publisher
    ..We measured the hypothalamic phosphorylation of two downstream targets of mTORC1, S6 kinase 1 (S6K1) and S6 ribosomal protein (S6), after administration of the FAS inhibitors C75 and cerulenin in rats...
  57. Wang F, Alain T, Szretter K, Stephenson K, Pol J, Atherton M, et al. S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3. Nat Immunol. 2016;17:514-522 pubmed publisher
    ..with DNA viruses induced interaction of the metabolic checkpoint kinase mTOR downstream effector and kinase S6K1 and the signaling adaptor STING in a manner dependent on the DNA sensor cGAS...
  58. Liu X, Yuan H, Niu Y, Niu W, Fu L. The role of AMPK/mTOR/S6K1 signaling axis in mediating the physiological process of exercise-induced insulin sensitization in skeletal muscle of C57BL/6 mice. Biochim Biophys Acta. 2012;1822:1716-26 pubmed publisher
    The crosstalk between mTORC1/S6K1 signaling and AMPK is emerging as a powerful and highly regulated way to gauge cellular energy and nutrient content...
  59. He G, Sung Y, DiGiovanni J, Fischer S. Thiazolidinediones inhibit insulin-like growth factor-i-induced activation of p70S6 kinase and suppress insulin-like growth factor-I tumor-promoting activity. Cancer Res. 2006;66:1873-8 pubmed
    ..skin keratinocytes was due to, at least partially, inhibition of IGF-I-induced phosphorylation of p70S6 kinase (p70S6K) at Thr(389), a site specifically phosphorylated by mammalian target of rapamycin (mTOR)...
  60. Uchiumi T, Fotovati A, Sasaguri T, Shibahara K, Shimada T, Fukuda T, et al. YB-1 is important for an early stage embryonic development: neural tube formation and cell proliferation. J Biol Chem. 2006;281:40440-9 pubmed
    ..These results demonstrate that YB-1 is involved in early mouse development, including neural tube closure and cell proliferation. ..
  61. Pelosi M, De Rossi M, Barberi L, Musaro A. IL-6 impairs myogenic differentiation by downmodulation of p90RSK/eEF2 and mTOR/p70S6K axes, without affecting AKT activity. Biomed Res Int. 2014;2014:206026 pubmed publisher
    ..IL-6 induces the activation of the Stat3 signaling and promotes the downmodulation of the p90RSK/eEF2 and mTOR/p70S6K axes, while it does not affect the activation of AKT...
  62. Ben Hur V, Denichenko P, Siegfried Z, Maimon A, KRAINER A, Davidson B, et al. S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1. Cell Rep. 2013;3:103-15 pubmed publisher
    Ribosomal S6 kinase 1 (S6K1) is a major mTOR downstream signaling molecule that regulates cell size and translation efficiency. Here, we report that short isoforms of S6K1 are overproduced in breast cancer cell lines and tumors...
  63. Vary T, Lang C. Differential phosphorylation of translation initiation regulators 4EBP1, S6k1, and Erk 1/2 following inhibition of alcohol metabolism in mouse heart. Cardiovasc Toxicol. 2008;8:23-32 pubmed publisher
    ..to examine the effects of inhibitors of ethanol metabolism on the phosphorylation of 4E-binding protein (4EBP1) and S6k1(Thr(389)), two factors regulating mRNA translation initiation...
  64. Zhang D, Liu J, Mi X, Liang Y, Li J, Huang C. The N-terminal region of p27 inhibits HIF-1α protein translation in ribosomal protein S6-dependent manner by regulating PHLPP-Ras-ERK-p90RSK axis. Cell Death Dis. 2014;5:e1535 pubmed publisher
    ..Although PI3K/AKT pathway was also involved in S6 activation, blocking AKT and p70S6K activation did not attenuate arsenite-induced S6 activation in p27-/- cells, suggesting p27 specifically targeted ..
  65. Cameron S, Ture S, Mickelsen D, Chakrabarti E, Modjeski K, McNitt S, et al. Platelet Extracellular Regulated Protein Kinase 5 Is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion. Circulation. 2015;132:47-58 pubmed publisher
    ..Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment. ..
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    ..regulators (including CCND1, CCND2, and ID2) and promotes cardiomyocyte growth through regulating expression of p70S6K. In addition, expression of multiple sarcomere proteins is altered in Mycn myocardial-inactivation embryos, ..
  67. Han S, Kim S, Bahl S, Li L, Burande C, Smith N, et al. The E3 ubiquitin ligase protein associated with Myc (Pam) regulates mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling in vivo through N- and C-terminal domains. J Biol Chem. 2012;287:30063-72 pubmed publisher
    ..The ubiquitin ligase complex containing Pam-Fbxo45 likely targets additional synaptic and axonal proteins, which may explain the overlapping neurodevelopmental defects observed in Phr1 and Fbxo45 deficiency. ..
  68. Medeiros C, Frederico M, Da Luz G, Pauli J, Silva A, Pinho R, et al. Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet-induced obesity rats. J Cell Physiol. 2011;226:666-74 pubmed publisher
    ..However, obesity and insulin resistance can alter mTOR/p70S6k. Exercise training is known to induce this pathway, but never in the heart of diet-induced obesity subjects...
  69. Tandon P, Gallo C, Khatri S, Barger J, Yepiskoposyan H, Plas D. Requirement for ribosomal protein S6 kinase 1 to mediate glycolysis and apoptosis resistance induced by Pten deficiency. Proc Natl Acad Sci U S A. 2011;108:2361-5 pubmed publisher
    ..We found that targeting ribosomal protein S6 kinase 1 (S6K1) in Pten-deficient cells suppressed glycolysis and induced apoptosis...
  70. Chen L, Jia J, Zhong W, Zhang Y, Lu J, Wang H, et al. [P70S6K is involved in the inhibition of testosterone production in TM3 mouse Leydig cells overexpressing Cox7a2]. Zhonghua Nan Ke Xue. 2011;17:291-5 pubmed
    ..of the steroidogenic acute regulatory protein (StAR) and the phosphorylation of the autophagy regulatory factor P70S6K were detected by Western blot...
  71. Sasaki C, Chen G, Munk R, Eitan E, Martindale J, Longo D, et al. p(⁷⁰S⁶K¹) in the TORC1 pathway is essential for the differentiation of Th17 Cells, but not Th1, Th2, or Treg cells in mice. Eur J Immunol. 2016;46:212-22 pubmed publisher
    ..Th17 cells in more detail, we compared the differentiation capacity of naïve T cells from wild type and p70(S6K1) knockout mice...
  72. Crossland H, Kazi A, Lang C, Timmons J, Pierre P, Wilkinson D, et al. Focal adhesion kinase is required for IGF-I-mediated growth of skeletal muscle cells via a TSC2/mTOR/S6K1-associated pathway. Am J Physiol Endocrinol Metab. 2013;305:E183-93 pubmed publisher
    ..We conclude that FAK is required for IGF-I-induced muscle hypertrophy, signaling through a TSC2/mTOR/S6K1-dependent pathway via means requiring the kinase activity of FAK but not altered FAK-TSC2 or FAK-Shp-2 binding.
  73. Oh C, Park S, Han J. Phospholipase D1 is required for lipopolysaccharide-induced tumor necrosis factor-? expression and production through S6K1/JNK/c-Jun pathway in Raw 264.7 cells. Cytokine. 2014;66:69-77 pubmed publisher
    ..Interestingly, only knockdown of PLD1 decreased TNF-? expression but not PLD2. Next, we investigated the S6K1-JNK-c-Jun signaling pathway in LPS-induced TNF-? expression mechanism...
  74. Hsieh C, Chuang J, Yang W, Yin Y, Lin Y. Ceramide inhibits insulin-stimulated Akt phosphorylation through activation of Rheb/mTORC1/S6K signaling in skeletal muscle. Cell Signal. 2014;26:1400-8 pubmed publisher
    ..Interestingly, we found that the phosphorylation of S6K at Thr389 was increased under the same conditions...
  75. Cao W, Manicassamy S, Tang H, Kasturi S, Pirani A, Murthy N, et al. Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3)K-mTOR-p70S6K pathway. Nat Immunol. 2008;9:1157-64 pubmed publisher
    ..Inhibition of mTOR or its 'downstream' mediators, the p70 ribosomal S6 protein kinases p70S6K1 and p70S6K2, during pDC activation by Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the ..
  76. Li J, Davidson G, Huang Y, Jiang B, Shi X, Costa M, et al. Nickel compounds act through phosphatidylinositol-3-kinase/Akt-dependent, p70(S6k)-independent pathway to induce hypoxia inducible factor transactivation and Cap43 expression in mouse epidermal Cl41 cells. Cancer Res. 2004;64:94-101 pubmed
    ..Ni(3)S(2) or NiCl(2) resulted in activation of phosphatidylinositol 3-kinase (PI-3K), Akt, and p70 S6 kinase (p70(S6k))...
  77. Csibi A, Cornille K, Leibovitch M, Poupon A, Tintignac L, Sanchez A, et al. The translation regulatory subunit eIF3f controls the kinase-dependent mTOR signaling required for muscle differentiation and hypertrophy in mouse. PLoS ONE. 2010;5:e8994 pubmed publisher
    ..muscle differentiation and hypertrophy by controlling the mammalian translational machinery via phosphorylation of S6K1 and 4E-BP1. mTOR and S6K1 are connected by interacting with the eIF3 initiation complex...
  78. Gong X, Zhang L, Huang T, Lin T, Miyares L, Wen J, et al. Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo. Hum Mol Genet. 2015;24:5746-58 pubmed publisher
    ..This was prevented by counteracting mTORC1 signaling through p70S6Ks (S6K1/2) or eukaryotic initiation factor 4E-binding protein (4E-BP1/2), which both regulate translation...
  79. Lebrun Julien F, Bachmann L, Norrmen C, Trötzmüller M, Köfeler H, Ruegg M, et al. Balanced mTORC1 activity in oligodendrocytes is required for accurate CNS myelination. J Neurosci. 2014;34:8432-48 pubmed publisher
    ..Our data demonstrate that a delicately balanced regulation of mTORC1 activation and action in oligodendrocytes is essential for CNS myelination, which has practical overtones for understanding CNS myelin disorders. ..
  80. Henkels K, Mallets E, Dennis P, Gomez Cambronero J. S6K is a morphogenic protein with a mechanism involving Filamin-A phosphorylation and phosphatidic acid binding. FASEB J. 2015;29:1299-313 pubmed publisher
    ..Here, we show that ribosomal S6K, which is normally considered a protein involved in protein translation, is a morphogenic protein...
  81. He J, Xu Q, Wang M, Li C, Qian X, Shi Z, et al. Oral administration of apigenin inhibits metastasis through AKT/P70S6K1/MMP-9 pathway in orthotopic ovarian tumor model. Int J Mol Sci. 2012;13:7271-82 pubmed publisher
    ..of apigenin in inhibiting metastasis, we found that apigenin greatly inhibited MMP-9 expression and p-AKT and p-p70S6K1 levels in the tumor tissues compared to the control group...
  82. Madala S, Thomas G, Edukulla R, Davidson C, Schmidt S, Schehr A, et al. p70 ribosomal S6 kinase regulates subpleural fibrosis following transforming growth factor-α expression in the lung. Am J Physiol Lung Cell Mol Physiol. 2016;310:L175-86 pubmed publisher
    The p70 ribosomal S6 kinase (S6K) is a downstream substrate that is phosphorylated and activated by the mammalian target of rapamycin complex and regulates multiple cellular processes associated with fibrogenesis...
  83. Martin T, Dennis M, Gordon B, Kimball S, Jefferson L. mTORC1 and JNK coordinate phosphorylation of the p70S6K1 autoinhibitory domain in skeletal muscle following functional overloading. Am J Physiol Endocrinol Metab. 2014;306:E1397-405 pubmed publisher
    The present project was designed to investigate phosphorylation of p70S6K1 in an animal model of skeletal muscle overload...