Genomes and Genes
Gene Symbol: S6k
Description: Ribosomal protein S6 kinase
Alias: 10539, 7-10, 7084, CG10539, DS6K, Dmel\CG10539, Dp70S6k, Dp70[s6k], Dp70s6k, Pk64F, Pk?6, S6K, S6K1, S6k, S6K, dS6K, dS6k, dp70[S6k], dp70s6k, dps6k, ds6k, fs(3)07084, l(3)07084, p-S6K, p70 S6K, p70/S6K, p70S6K, p70[S6 kinase], p70[S6K], p70[S6k], p70[S6kinase], p70s6K, s6k, s6k11, ribosomal protein S6 kinase, CG10539-PA, CG10539-PB, RPS6-p70-protein kinase, S6 kinase, S6-kinase, S6K kinase, S6k-PA, S6k-PB, S6kinase, dS6 kinase, p70 S6 kinase, p70 S6 kinase 1, p70 ribosomal S6 kinase, p70S6 kinase, p70S6K kinase, protein kinase-like 64F, ribosomal S6 protein kinase
Species: fruit fly
- Hietakangas V, Cohen S. Re-evaluating AKT regulation: role of TOR complex 2 in tissue growth. Genes Dev. 2007;21:632-7 pubmed..Thus, TORC2 acts as a rheostat to broaden the range of AKT signaling at the high end of its range. ..
- Sun P, Quan Z, Zhang B, Wu T, Xi R. TSC1/2 tumour suppressor complex maintains Drosophila germline stem cells by preventing differentiation. Development. 2010;137:2461-9 pubmed publisher..The GSC loss can be rescued by treatment with TORC1 inhibitor rapamycin, or by eliminating S6K, a TORC1 downstream effecter, suggesting that precocious differentiation of Tsc1/2 mutant GSC is due to ..
- Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung R, et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol. 2002;4:699-704 pubmedTarget of Rapamycin (TOR) mediates a signalling pathway that couples amino acid availability to S6 kinase (S6K) activation, translational initiation and cell growth...
- Hall D, Grewal S, de la Cruz A, Edgar B. Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila. BMC Biol. 2007;5:10 pubmed..The effect of insulin signaling upon TOR activity varies according to cellular type and context. ..
- Hennig K, Colombani J, Neufeld T. TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J Cell Biol. 2006;173:963-74 pubmed..Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling...
- Gingras A, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15:807-26 pubmed
- Grewal S, Evans J, Edgar B. Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway. J Cell Biol. 2007;179:1105-13 pubmed..Stimulation of rRNA synthesis by TIF-IA may therefore provide a feed-forward mechanism to coregulate the levels of other ribosome components. ..
- Wessells R, Fitzgerald E, Piazza N, Ocorr K, Morley S, Davies C, et al. d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila. Aging Cell. 2009;8:542-52 pubmed publisher..Another effector of dTOR and insulin signaling, dS6K, may influence cardiac aging nonautonomously through its activity in the insulin-producing cells, possibly by ..
- Liu S, Lu B. Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster. PLoS Genet. 2010;6:e1001237 pubmed publisher..Here we show that PINK1 genetically interacted with the protein translation pathway. Enhanced translation through S6K activation significantly exacerbated PINK1 mutant phenotypes, whereas reduction of translation showed suppression...
- Stocker H, Radimerski T, Schindelholz B, Wittwer F, Belawat P, Daram P, et al. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat Cell Biol. 2003;5:559-65 pubmed..that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth, and that a major effector of Rheb function is ribosomal S6 kinase (S6K).
- Schleich S, Teleman A. Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth. PLoS ONE. 2009;4:e6305 pubmed publisher..This shows that phosphorylation of the Tsc1/2 complex by Akt is not required for Akt to activate TORC1 and to promote tissue growth in Drosophila. ..
- Miron M, Lasko P, Sonenberg N. Signaling from Akt to FRAP/TOR targets both 4E-BP and S6K in Drosophila melanogaster. Mol Cell Biol. 2003;23:9117-26 pubmed..Their binding to eIF4E is reversed by phosphorylation of several key Ser/Thr residues. In Drosophila, S6 kinase (dS6K) and a single 4E-BP (d4E-BP) are phosphorylated via the insulin and target of rapamycin (TOR) signaling ..
- Scott R, Juhasz G, Neufeld T. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr Biol. 2007;17:1-11 pubmed..Furthermore, this work identifies autophagy as a critical mechanism by which inhibition of TOR signaling leads to reduced cell growth. ..
- Kim E, Goraksha Hicks P, Li L, Neufeld T, Guan K. Regulation of TORC1 by Rag GTPases in nutrient response. Nat Cell Biol. 2008;10:935-45 pubmed publisher..Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals. ..
- Findlay G, Yan L, Procter J, Mieulet V, Lamb R. A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007;403:13-20 pubmed..pathway in Drosophila we have identified a Ste20 family member (MAP4K3) that is required for maximal S6K (S6 kinase)/4E-BP1 [eIF4E (eukaryotic initiation factor 4E)-binding protein 1] phosphorylation and regulates cell growth...
- Dearolf C. Fruit fly "leukemia". Biochim Biophys Acta. 1998;1377:M13-23 pubmed
- Goberdhan D, Meredith D, Boyd C, Wilson C. PAT-related amino acid transporters regulate growth via a novel mechanism that does not require bulk transport of amino acids. Development. 2005;132:2365-75 pubmed..In a heterologous Xenopus oocyte system, PATH also activates the TOR target S6 kinase in an amino acid-dependent way...
- Manning B, Cantley L. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci. 2003;28:573-6 pubmed
- Penney J, Tsurudome K, Liao E, Elazzouzi F, Livingstone M, González M, et al. TOR is required for the retrograde regulation of synaptic homeostasis at the Drosophila neuromuscular junction. Neuron. 2012;74:166-78 pubmed publisher..Our findings suggest that cap-dependent translation under the control of TOR plays a critical role in establishing the activity dependent homeostatic response at the NMJ. ..
- Day S, Lawrence P. Measuring dimensions: the regulation of size and shape. Development. 2000;127:2977-87 pubmed..We discuss a hypothesis that the local steepness of a morphogen gradient is a measure of length in one axis, a measure that is used to determine whether there will be net growth or not. ..
- Pan D, Dong J, Zhang Y, Gao X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol. 2004;14:78-85 pubmed..Here, we review these exciting developments with an emphasis on Drosophila studies and discuss how Drosophila can be a powerful model system for an understanding of the molecular mechanisms of the activity of human disease genes. ..
- Zhang H, Stallock J, Ng J, Reinhard C, Neufeld T. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 2000;14:2712-24 pubmed..As in mammalian cells, the kinase activity of dTOR is required for growth factor-dependent phosphorylation of p70 S6 kinase (p70(S6K)) in vitro, and we demonstrate that overexpression of p70(S6K) in vivo can rescue dTOR mutant animals ..
- McNeill H, Craig G, Bateman J. Regulation of neurogenesis and epidermal growth factor receptor signaling by the insulin receptor/target of rapamycin pathway in Drosophila. Genetics. 2008;179:843-53 pubmed publisher..TOR regulates growth by controlling the activity of S6 kinase (S6K) and eIF4E...
- Potter C, Pedraza L, Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol. 2002;4:658-65 pubmed..Furthermore, all Akt/PKB growth signals are blocked by expression of a Tsc2 mutant lacking Akt phosphorylation sites. Thus, Tsc2 seems to be the critical target of Akt in mediating growth signals for the insulin signalling pathway. ..
- Radimerski T, Montagne J, Rintelen F, Stocker H, van der Kaay J, Downes C, et al. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat Cell Biol. 2002;4:251-5 pubmed..Effectors of this pathway include Chico (the insulin receptor substrate homologue), dPI(3)K, dPKB, dPTEN, and dS6K. Mutations in any of these components have a striking effect on cell size and number, with the exception of dS6K...
- Tapon N, Ito N, Dickson B, Treisman J, Hariharan I. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell. 2001;105:345-55 pubmed..In postmitotic mutant cells, levels of Cyclin E and Cyclin A are elevated. This correlates with a tendency for these cells to reenter the cell cycle inappropriately as is observed in the human lesions. ..
- Patel P, Tamanoi F. Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. J Cell Sci. 2006;119:4285-92 pubmed..The well-conserved Rheb-Target-of-rapamycin (TOR)-S6-kinase (S6K) signaling pathway regulates several cellular processes and has been shown to influence lifespan and diseases such ..
- Oldham S, Montagne J, Radimerski T, Thomas G, Hafen E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 2000;14:2689-94 pubmed..dTOR impinges on the insulin signaling pathway by autonomously affecting growth through modulating the activity of dS6K. However, in contrast to other components in the insulin signaling pathway, partial loss of dTOR function ..
- Lizcano J, Alrubaie S, Kieloch A, Deak M, Leevers S, Alessi D. Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B. Biochem J. 2003;374:297-306 pubmed..mechanism by which insulin regulates cell growth and protein synthesis is through activation of the p70 ribosomal S6 protein kinase (S6K)...
- Zhang Y, Gao X, Saucedo L, Ru B, Edgar B, Pan D. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol. 2003;5:578-81 pubmed..Point mutations in the GAP domain of Tsc2 disrupted its ability to regulate Rheb without affecting the ability of Tsc2 to form a complex with Tsc1. Our studies identify Rheb as a molecular target of the TSC tumour suppressors. ..
- Sun X, Komatsu T, Lim J, Laslo M, Yolitz J, Wang C, et al. Nutrient-dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster. Aging Cell. 2012;11:783-93 pubmed publisher..sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling...
- Dong J, Pan D. Tsc2 is not a critical target of Akt during normal Drosophila development. Genes Dev. 2004;18:2479-84 pubmed..Strikingly, such mutants completely rescue the lethality and cell growth defects of Tsc2-null mutants. Taken together, our data suggest that Tsc2 is not a critical substrate of Akt in normal Drosophila development. ..
- Cheng L, Bailey A, Leevers S, Ragan T, Driscoll P, Gould A. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell. 2011;146:435-47 pubmed publisher..Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors. ..
- Georgiev P, Okkenhaug H, Drews A, Wright D, Lambert S, Flick M, et al. TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development. Cell Metab. 2010;12:386-397 pubmed publisher..We propose that regulation of Zn(2+) homeostasis through dTRPM channels is required to support molecular processes that mediate class I PI3K-regulated cell growth. ..
- Radimerski T, Mini T, Schneider U, Wettenhall R, Thomas G, Jeno P. Identification of insulin-induced sites of ribosomal protein S6 phosphorylation in Drosophila melanogaster. Biochemistry. 2000;39:5766-74 pubmed..The importance of these observations in cell growth and development is discussed. ..
- Howlett E, Lin C, Lavery W, Stern M. A PI3-kinase-mediated negative feedback regulates neuronal excitability. PLoS Genet. 2008;4:e1000277 pubmed publisher..Finally, we show that PI3K increases both axon diameter and synapse number via the Tor/S6 kinase pathway, but not Foxo...
- Zhang W, Thompson B, Hietakangas V, Cohen S. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila. PLoS Genet. 2011;7:e1002429 pubmed publisher..The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels. ..
- Pritchett T, McCall K. Role of the insulin/Tor signaling network in starvation-induced programmed cell death in Drosophila oogenesis. Cell Death Differ. 2012;19:1069-79 pubmed publisher..Furthermore, starvation-induced PCD is regulated by Tor signaling converging with the canonical insulin signaling pathway. ..
- Teleman A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem J. 2009;425:13-26 pubmed publisher..I discuss both the intracellular signalling network, as well as the communication between organs in the fly. ..
- Bjedov I, Toivonen J, Kerr F, Slack C, Jacobson J, Foley A, et al. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 2010;11:35-46 pubmed publisher..Rapamycin could increase life span of weak insulin/Igf signaling (IIS) pathway mutants and of flies with life span maximized by dietary restriction, indicating additional mechanisms. ..
- Potter C, Xu T. Mechanisms of size control. Curr Opin Genet Dev. 2001;11:279-86 pubmed..The mechanisms of organ size control could also be critical targets for evolutionary events or disease processes such as tumorigenesis. ..
- Birse R, Choi J, Reardon K, Rodriguez J, Graham S, Diop S, et al. High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila. Cell Metab. 2010;12:533-44 pubmed publisher..We conclude that deregulation of insulin-TOR signaling due to a HFD is responsible for mediating the detrimental effects on metabolism and heart function. ..
- Stocker H, Hafen E. Genetic control of cell size. Curr Opin Genet Dev. 2000;10:529-35 pubmed..Evidence is emerging for a signalling cascade conserved in evolution that links external nutrient sources to cell size. ..
- Tang H, Smith Caldas M, Driscoll M, Salhadar S, Shingleton A. FOXO regulates organ-specific phenotypic plasticity in Drosophila. PLoS Genet. 2011;7:e1002373 pubmed publisher..These data indicate that the extent of phenotypic plasticity may be modified by changes in the expression of genes involved in signaling environmental information to developmental processes. ..
- Montagne J, Stewart M, Stocker H, Hafen E, Kozma S, Thomas G. Drosophila S6 kinase: a regulator of cell size. Science. 1999;285:2126-9 pubmed..Drosophila deficient in the S6 kinase gene (dS6K) exhibited an extreme delay in development and a severe reduction in body size...
- Kockel L, Kerr K, Melnick M, Brückner K, Hebrok M, Perrimon N. Dynamic switch of negative feedback regulation in Drosophila Akt-TOR signaling. PLoS Genet. 2010;6:e1000990 pubmed publisher..Whereas in cell culture dAkt is regulated by S6 Kinase (S6K)-dependent negative feedback, this feedback inhibition only plays a minor role in vivo...
- Stewart M, Berry C, Zilberman F, Thomas G, Kozma S. The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity. Proc Natl Acad Sci U S A. 1996;93:10791-6 pubmed..Consistent with this observation, analysis of total S6 kinase activity in fractionated Drosophila Schneider line 2 cell extracts reveals two peaks of activity, only one of ..
- Reiling J, Hafen E. The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev. 2004;18:2879-92 pubmed..In Drosophila, the insulin receptor/TOR/S6K signaling network plays a fundamental role in the control of metabolism and cell growth...
- Lee S, Kim S, Lee J, Park J, Lee G, Kim Y, et al. ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase. EMBO Rep. 2007;8:360-5 pubmed..an autophagy-regulating kinase, and found that ATG1 is a negative regulator of the target of rapamycin (TOR)/S6 kinase (S6K) pathway...
- Radimerski T, Montagne J, Hemmings Mieszczak M, Thomas G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 2002;16:2627-32 pubmed..Here, we show that absence of Drosophila Tsc1/2 leads to constitutive dS6K activation and inhibition of dPKB, the latter effect being relieved by loss of dS6K...
- Dar A, Das T, Shokat K, Cagan R. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature. 2012;486:80-4 pubmed publisher..Inhibition of Ret plus Raf, Src and S6K was required for optimal animal survival, whereas inhibition of the 'anti-target' Tor led to toxicity owing to ..
- Wang T, Lao U, Edgar B. TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J Cell Biol. 2009;186:703-11 pubmed publisher..Thus, our data indicate that TOR induces cell death by suppressing autophagy and provide direct genetic evidence that autophagy alleviates cell death in several common types of neurodegenerative disease. ..
- Sarbassov D, Guertin D, Ali S, Sabatini D. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307:1098-101 pubmed..Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation. ..
- Bateman J, McNeill H. Temporal control of differentiation by the insulin receptor/tor pathway in Drosophila. Cell. 2004;119:87-96 pubmed..Examination of InR, PI3K, PTEN, Tor, Rheb, and S6 kinase mutants demonstrates that increased InR signaling leads to precocious differentiation while decreased signaling ..
- Hsu Y, Chern J, Cai Y, Liu M, Choi K. Drosophila TCTP is essential for growth and proliferation through regulation of dRheb GTPase. Nature. 2007;445:785-8 pubmed..dTCTP is genetically epistatic to Tsc1 and dRheb, but acts upstream of dS6k, a downstream target of dRheb...
- Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol. 2003;13:79-85 pubmed..This review summarizes current studies primarily from Drosophila regarding the function of the insulin/IGF system in the control of growth. ..
- Bielinski V, Mumby M. Functional analysis of the PP2A subfamily of protein phosphatases in regulating Drosophila S6 kinase. Exp Cell Res. 2007;313:3117-26 pubmedPhosphorylation and activation of ribosomal S6 protein kinase is an important link in the regulation of cell size by the target of rapamycin (TOR) protein kinase...
- Chang Y, Neufeld T. An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell. 2009;20:2004-14 pubmed publisher..Atg1-Atg13 complexes thus function at multiple levels to mediate and adjust nutrient-dependent autophagic signaling. ..
- Vargas M, Luo N, Yamaguchi A, Kapahi P. A role for S6 kinase and serotonin in postmating dietary switch and balance of nutrients in D. melanogaster. Curr Biol. 2010;20:1006-11 pubmed publisher..We also demonstrate that S6 kinase (S6K) and serotonin production are involved in the postmating dietary switch...
- Saucedo L, Gao X, Chiarelli D, Li L, Pan D, Edgar B. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol. 2003;5:566-71 pubmed..Levels of rheb mRNA are rapidly induced in response to protein starvation, and overexpressed Rheb can drive cell growth in starved animals, suggesting a role for Rheb in the nutritional control of cell growth. ..
- Knox S, Ge H, Dimitroff B, Ren Y, Howe K, Arsham A, et al. Mechanisms of TSC-mediated control of synapse assembly and axon guidance. PLoS ONE. 2007;2:e375 pubmed..Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1 effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1 mosaics, while reductions in Tor function suppressed ..
- Rintelen F, Stocker H, Thomas G, Hafen E. PDK1 regulates growth through Akt and S6K in Drosophila. Proc Natl Acad Sci U S A. 2001;98:15020-5 pubmed..Here we show that, in Drosophila, dPDK1 controls cellular and organism growth by activating dAkt and S6 kinase, dS6K...
- Potter C, Huang H, Xu T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell. 2001;105:357-68 pubmed..Genetic epistasis data are consistent with a model that Tsc1 and Tsc2 function together in the insulin signaling pathway...
- Oldham S, Bohni R, Stocker H, Brogiolo W, Hafen E. Genetic control of size in Drosophila. Philos Trans R Soc Lond B Biol Sci. 2000;355:945-52 pubmed..In this article we will review recent evidence from vertebrates and particularly from Drosophila that implicates insulin/insulin-like growth factor-I and other growth pathways in the control of cell, organ and body size. ..
- Shen W, Ganetzky B. Autophagy promotes synapse development in Drosophila. J Cell Biol. 2009;187:71-9 pubmed publisher..Because autophagy is triggered in response to many environmental cues, our findings suggest that it is perfectly positioned to link environmental conditions with synaptic growth and plasticity. ..