mTOR

Summary

Gene Symbol: mTOR
Description: mechanistic target of rapamycin kinase
Alias: FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS, serine/threonine-protein kinase mTOR, FK506 binding protein 12-rapamycin associated protein 2, FK506-binding protein 12-rapamycin complex-associated protein 1, FKBP-rapamycin associated protein, FKBP12-rapamycin complex-associated protein 1, mammalian target of rapamycin, mechanistic target of rapamycin (serine/threonine kinase), rapamycin and FKBP12 target 1, rapamycin associated protein FRAP2, rapamycin target protein 1
Species: human
Products:     mTOR

Top Publications

  1. Zhou H, Huang S. The complexes of mammalian target of rapamycin. Curr Protein Pept Sci. 2010;11:409-24 pubmed
    The mammalian target of rapamycin (mTOR) has attracted substantial attention because of its involvement in a variety of diseases, such as cancer, cardiac hypertrophy, diabetes and obesity...
  2. García Martínez J, Moran J, Clarke R, Gray A, Cosulich S, Chresta C, et al. Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). Biochem J. 2009;421:29-42 pubmed publisher
    mTOR (mammalian target of rapamycin) stimulates cell growth by phosphorylating and promoting activation of AGC (protein kinase A/protein kinase G/protein kinase C) family kinases such as Akt (protein kinase B), S6K (p70 ribosomal S6 ..
  3. Jung C, Jun C, Ro S, Kim Y, Otto N, Cao J, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20:1992-2003 pubmed publisher
    ..Although mammalian target of rapamycin (mTOR) is known as the key regulator of autophagy induction, the mechanism by which mTOR regulates ..
  4. Kang M, Reynolds C, Maris J, Gorlick R, Kolb E, Lock R, et al. Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2014;61:1486-9 pubmed publisher
    MLN0128 is an investigational small molecule ATP-competitive inhibitor of the serine/threonine kinase mTOR. MLN0128 was tested against the in vitro panel at concentrations ranging from 0...
  5. Flinn R, Yan Y, Goswami S, Parker P, Backer J. The late endosome is essential for mTORC1 signaling. Mol Biol Cell. 2010;21:833-41 pubmed publisher
    ..or knockdown of the Rab7 GEF hVps39, insulin- and amino acid-stimulated mTORC1/S6K1 activation were inhibited, and mTOR localized to hybrid early/late endosomes...
  6. Ha S, Kim D, Kim I, Kim J, Lee M, Lee H, et al. PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals. Cell Signal. 2006;18:2283-91 pubmed
    Mammalian target-of-rapamycin (mTOR), which is a master controller of cell growth, senses a mitogenic signal in part through the lipid second messenger phosphatidic acid (PA), generated by phospholipase D (PLD)...
  7. Naegele S, Morley S. Molecular cross-talk between MEK1/2 and mTOR signaling during recovery of 293 cells from hypertonic stress. J Biol Chem. 2004;279:46023-34 pubmed
  8. Dowling R, Zakikhani M, Fantus I, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007;67:10804-12 pubmed
    ..The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-..
  9. Li W, Tan D, Zhang Z, Liang J, Brown R. Activation of Akt-mTOR-p70S6K pathway in angiogenesis in hepatocellular carcinoma. Oncol Rep. 2008;20:713-9 pubmed
    Angiogenesis is an essential process for progression of hepatocellular carcinoma (HCC). The Akt-mTOR-p70S6K signal pathway has been recognized for its roles in regulating neoangiogenesis...

More Information

Publications216 found, 100 shown here

  1. Dhillon T, Mauri F, Bellezza G, Cagini L, Barbareschi M, North B, et al. Overexpression of the mammalian target of rapamycin: a novel biomarker for poor survival in resected early stage non-small cell lung cancer. J Thorac Oncol. 2010;5:314-9 pubmed publisher
    ..Here, we investigate whether the immunohistochemical expression of a key kinase implicated in lung cancer biology, the mammalian target of rapamycin (mTOR) can predict survival outcome in patients with early stage resected NSCLC.
  2. Frias M, Thoreen C, Jaffe J, Schroder W, Sculley T, Carr S, et al. mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol. 2006;16:1865-70 pubmed
    The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that participates in at least two distinct multiprotein complexes, mTORC1 and mTORC2 ...
  3. 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
    The mTOR (mammalian target of rapamycin) signalling pathway is a key regulator of cell growth and is controlled by growth factors and nutrients such as amino acids...
  4. Lafay Chebassier C, Paccalin M, Page G, Barc Pain S, Perault Pochat M, Gil R, et al. mTOR/p70S6k signalling alteration by Abeta exposure as well as in APP-PS1 transgenic models and in patients with Alzheimer's disease. J Neurochem. 2005;94:215-25 pubmed
    ..Translational control includes phosphorylation of the kinases mammalian target of rapamycin (mTOR) and p70S6k which modulate cell growth, proliferation and autophagy...
  5. Copp J, Manning G, Hunter T. TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 2009;69:1821-7 pubmed publisher
    The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic component of two evolutionarily conserved signaling complexes. mTOR signaling complex 1 (mTORC1) is a key regulator of growth factor and nutrient signaling...
  6. Perotti A, Locatelli A, Sessa C, Hess D, Viganò L, Capri G, et al. Phase IB study of the mTOR inhibitor ridaforolimus with capecitabine. J Clin Oncol. 2010;28:4554-61 pubmed publisher
    ..applicability of fluoropyrimidines in solid tumors prompted the study of the combination of the mammalian target of rapamycin (mTOR) inhibitor, non-prodrug rapamycin analog ridaforolimus, with capecitabine...
  7. Aslan J, Tormoen G, Loren C, Pang J, McCarty O. S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation. Blood. 2011;118:3129-36 pubmed publisher
    ..Here, we identify a role for the ribosome protein S6 kinase (S6K1) and its upstream regulator mTOR in the control of platelet activation and aggregate formation under shear flow...
  8. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg M, Hall A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol. 2004;6:1122-8 pubmed
    ..Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor...
  9. Lee J, Huynh M, Silhavy J, Kim S, Dixon Salazar T, Heiberg A, et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat Genet. 2012;44:941-5 pubmed publisher
    ..S6 protein phosphorylation in the brains of affected individuals, indicating aberrant activation of mammalian target of rapamycin (mTOR) signaling...
  10. Hsieh A, Liu Y, Edlind M, Ingolia N, Janes M, Sher A, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012;485:55-61 pubmed publisher
    The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer...
  11. Kim J, Chen J. Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation. Proc Natl Acad Sci U S A. 2000;97:14340-5 pubmed
    ..FKBP12-rapamycin-associated protein (FRAP; also named mTOR or RAFT1), a member of the ataxia telangiectasia mutated (ATM)-related kinase family, governs a rapamycin-sensitive ..
  12. Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, et al. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells. 2004;9:359-66 pubmed
    The mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that plays a crucial role in a nutrient-sensitive signalling pathway that regulates cell growth...
  13. Li S, Huang E, Lu H, Huang W, Yen C, Huang W, et al. Phosphorylated mammalian target of rapamycin expression is associated with the response to chemoradiotherapy in patients with esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg. 2012;144:1352-9, 1359.e1 pubmed publisher
    The mammalian target of rapamycin signaling pathway has been implicated in therapeutic resistance in several types of cancer...
  14. Pearce L, Huang X, Boudeau J, Pawłowski R, Wullschleger S, Deak M, et al. Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J. 2007;405:513-22 pubmed
    The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth...
  15. Reynolds T, Bodine S, Lawrence J. Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem. 2002;277:17657-62 pubmed
    ..amino acids, and the degree of muscle loading on the phosphorylation of Ser(2448), a site in the mammalian target of rapamycin (mTOR) phosphorylated by protein kinase B (PKB) in vitro...
  16. Long X, Ortiz Vega S, Lin Y, Avruch J. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem. 2005;280:23433-6 pubmed
    The removal of extracellular amino acids or leucine alone inhibits the ability of the mammalian target of rapamycin (mTOR) to signal to the raptor-dependent substrates, p70 S6 kinase and 4E-BP...
  17. Long X, Lin Y, Ortiz Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol. 2005;15:702-13 pubmed
    ..to the TOR complex specifically, independently of its ability to bind TSC2, through separate interactions with the mTOR catalytic domain and with LST8...
  18. An J, Kim K, Choi M, Noh J, Sohn T, Bae J, et al. Prognostic role of p-mTOR expression in cancer tissues and metastatic lymph nodes in pT2b gastric cancer. Int J Cancer. 2010;126:2904-13 pubmed publisher
    Despite the great interest in mammalian target of rapamycin (mTOR) as a potential anticancer therapy target, the prognostic role of mTOR in gastric cancer has not been elucidated...
  19. Avila Flores A, Santos T, Rincón E, Merida I. Modulation of the mammalian target of rapamycin pathway by diacylglycerol kinase-produced phosphatidic acid. J Biol Chem. 2005;280:10091-9 pubmed
    The protein known as mammalian target of rapamycin (mTOR) regulates cell growth by integrating different stimuli, such as available nutrients and mitogenic factors...
  20. Liu E, Knutzen C, Krauss S, Schweiger S, Chiang G. Control of mTORC1 signaling by the Opitz syndrome protein MID1. Proc Natl Acad Sci U S A. 2011;108:8680-5 pubmed publisher
    ..Increased PP2A levels, resulting from proteasome inhibition or depletion of MID1, lead to disruption of the mTOR/Raptor complex and down-regulated mTORC1 signaling...
  21. Rosner M, Siegel N, Valli A, Fuchs C, Hengstschlager M. mTOR phosphorylated at S2448 binds to raptor and rictor. Amino Acids. 2010;38:223-8 pubmed publisher
    In mammalian cells, the mammalian target of rapamycin (mTOR) forms an enzyme complex with raptor (together with other proteins) named mTOR complex 1 (mTORC1), of which a major target is the p70 ribosomal protein S6 kinase (p70S6K)...
  22. Ng T, Leprivier G, Robertson M, Chow C, Martin M, Laderoute K, et al. The AMPK stress response pathway mediates anoikis resistance through inhibition of mTOR and suppression of protein synthesis. Cell Death Differ. 2012;19:501-10 pubmed publisher
    ..However, AMPK activation represses the mTOR complex-1 (mTORC1) pathway only in transformed cells, suggesting a key role for AMPK-mediated mTORC1 inhibition in ..
  23. Yang Q, Inoki K, Ikenoue T, Guan K. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes Dev. 2006;20:2820-32 pubmed
    ..It also disrupts the interaction between Rictor and mTOR. Furthermore, Sin1 is required for TORC2 kinase activity in vitro...
  24. Martina J, Chen Y, Gucek M, Puertollano R. MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy. 2012;8:903-14 pubmed publisher
    The mammalian target of rapamycin (MTOR) protein kinase complex is a key component of a pathway that regulates cell growth and proliferation in response to energy levels, hypoxia, nutrients and insulin...
  25. Goh E, Pardo O, Michael N, Niewiarowski A, Totty N, Volkova D, et al. Involvement of heterogeneous ribonucleoprotein F in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway. J Biol Chem. 2010;285:17065-76 pubmed publisher
    ..Signaling via the phosphotidylinositol 3-kinase and mammalian target of rapamycin (mTOR) pathways is critical in regulating the activity and subcellular localization of S6Ks...
  26. Kwak D, Choi S, Jeong H, Jang J, Lee Y, Jeon H, et al. Osmotic stress regulates mammalian target of rapamycin (mTOR) complex 1 via c-Jun N-terminal Kinase (JNK)-mediated Raptor protein phosphorylation. J Biol Chem. 2012;287:18398-407 pubmed publisher
    b>mTOR complex 1 (mTORC1) is a multiprotein complex that integrates diverse signals including growth factors, nutrients, and stress to control cell growth...
  27. Brown E, Albers M, Shin T, Ichikawa K, Keith C, Lane W, et al. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature. 1994;369:756-8 pubmed
    ..Here we isolate a mammalian FKBP-rapamycin-associated protein (FRAP) whose binding to structural variants of rapamycin complexed to FKBP12 correlates with the ability of these ligands ..
  28. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo J, Bonenfant D, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell. 2002;10:457-68 pubmed
    ..Thus, the distinct TOR complexes account for the diversity, specificity, and selective rapamycin inhibition of TOR signaling. TORC1 and possibly TORC2 are conserved from yeast to man. ..
  29. Feng Z. p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment. Cold Spring Harb Perspect Biol. 2010;2:a001057 pubmed publisher
    ..These include the down-regulation of two central cell-growth pathways, the IGF/AKT-1 and mTOR pathways, and the up-regulation of the activities of the endosomal compartment...
  30. Lin J, Wang J, Greisinger A, Grossman H, Forman M, Dinney C, et al. Energy balance, the PI3K-AKT-mTOR pathway genes, and the risk of bladder cancer. Cancer Prev Res (Phila). 2010;3:505-17 pubmed publisher
    ..energy balance and risk of bladder cancer and assessed the joint effects of genetic variants in the mammalian target of rapamycin (mTOR) pathway genes with energy balance...
  31. Schieke S, Phillips D, McCoy J, Aponte A, Shen R, Balaban R, et al. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem. 2006;281:27643-52 pubmed
    ..Here we demonstrate that in mammalian cells the mammalian TOR (mTOR) pathway plays a significant role in determining both resting oxygen consumption and oxidative capacity...
  32. Alexander A, Cai S, Kim J, Nanez A, Sahin M, Maclean K, et al. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A. 2010;107:4153-8 pubmed publisher
  33. Santiskulvong C, Konecny G, Fekete M, Chen K, Karam A, Mulholland D, et al. Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma. Clin Cancer Res. 2011;17:2373-84 pubmed publisher
    This study evaluates the effect of dual PI3K and mTOR inhibition using NVP-BEZ235 in preclinical models of ovarian cancer as a potential novel therapeutic strategy...
  34. Dan H, Cooper M, Cogswell P, Duncan J, Ting J, Baldwin A. Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. Genes Dev. 2008;22:1490-500 pubmed publisher
    ..A key effector of Akt-induced signaling is the regulatory protein mTOR (mammalian target of rapamycin)...
  35. Maehama T, Tanaka M, Nishina H, Murakami M, Kanaho Y, Hanada K. RalA functions as an indispensable signal mediator for the nutrient-sensing system. J Biol Chem. 2008;283:35053-9 pubmed publisher
    ..RalA and its activator RalGDS participate in nutrient sensing and are indispensable for activation of mammalian target of rapamycin complex 1 (mTORC1) induced by extracellular nutrients...
  36. Chiu M, Katz H, Berlin V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci U S A. 1994;91:12574-8 pubmed
    ..Specific interactors, designated RAPT1, encode overlapping sequences homologous to yeast Tor, a putative novel phosphatidylinositol 3-kinase...
  37. Chiang G, Abraham R. Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase. J Biol Chem. 2005;280:25485-90 pubmed
    The mammalian target of rapamycin (mTOR) coordinates cell growth with the growth factor and nutrient/energy status of the cell...
  38. Wang Y, Mikhailova M, Bose S, Pan C, deVere White R, Ghosh P. Regulation of androgen receptor transcriptional activity by rapamycin in prostate cancer cell proliferation and survival. Oncogene. 2008;27:7106-17 pubmed publisher
    The mTOR (mammalian target of rapamycin) inhibitor rapamycin caused growth arrest in both androgen-dependent and androgen-independent prostate cancer cells; however, long-term treatment induced resistance to the drug...
  39. Schmitz F, Heit A, Dreher S, Eisenächer K, Mages J, Haas T, et al. Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells. Eur J Immunol. 2008;38:2981-92 pubmed publisher
    The mammalian target of rapamycin (mTOR) can be viewed as cellular master complex scoring cellular vitality and stress. Whether mTOR controls also innate immune-defenses is currently unknown...
  40. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009;136:521-34 pubmed publisher
    Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy...
  41. Weyrich A, Denis M, Schwertz H, Tolley N, Foulks J, Spencer E, et al. mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. Blood. 2007;109:1975-83 pubmed
    ..that activated human platelets synthesize B-cell lymphoma-3 (Bcl-3) under translational control by mammalian target of rapamycin (mTOR)...
  42. Sancak Y, Peterson T, Shaul Y, Lindquist R, Thoreen C, Bar Peled L, et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008;320:1496-501 pubmed publisher
    ..The Rag proteins do not directly stimulate the kinase activity of mTORC1, but, like amino acids, promote the intracellular localization of mTOR to a compartment that also contains its activator Rheb.
  43. Tanaka K, Babic I, Nathanson D, Akhavan D, Guo D, Gini B, et al. Oncogenic EGFR signaling activates an mTORC2-NF-?B pathway that promotes chemotherapy resistance. Cancer Discov. 2011;1:524-38 pubmed publisher
    Although it is known that mTOR complex 2 (mTORC2) functions upstream of Akt, the role of this protein kinase complex in cancer is not well understood...
  44. Zhu M, Yu H, Shi T, He J, Wang M, Li Q, et al. Polymorphisms in mTORC1 genes modulate risk of esophageal squamous cell carcinoma in eastern Chinese populations. J Thorac Oncol. 2013;8:788-95 pubmed publisher
    b>Mammalian target of rapamycin complex 1 (mTORC1) is an evolutionary conserved multiprotein complex that functions as a key regulator of gene transcription, protein translation, and autophagy...
  45. Choi J, Chen J, Schreiber S, Clardy J. Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science. 1996;273:239-42 pubmed
    ..agent, binds two proteins: the FK506-binding protein (FKBP12) and the FKBP-rapamycin-associated protein (FRAP)...
  46. Corradetti M, Inoki K, Guan K. The stress-inducted proteins RTP801 and RTP801L are negative regulators of the mammalian target of rapamycin pathway. J Biol Chem. 2005;280:9769-72 pubmed
    The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays an essential role in cell growth control...
  47. Holz M, Blenis J. Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase. J Biol Chem. 2005;280:26089-93 pubmed
    Here we demonstrate that mammalian target of rapamycin (mTOR) is phosphorylated in a rapamycin-sensitive manner. We show that S6 kinase 1 (S6K1), but not Akt, directly phosphorylates mTOR in cell-free in vitro system and in cells...
  48. Nagaraja A, Creighton C, Yu Z, Zhu H, Gunaratne P, Reid J, et al. A link between mir-100 and FRAP1/mTOR in clear cell ovarian cancer. Mol Endocrinol. 2010;24:447-63 pubmed publisher
    ..the critical roles of the phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1/mammalian target of rapamycin (mTOR) pathway in clear cell ovarian cancer, we focused on mir-100, a putative tumor suppressor that ..
  49. Bridges D, Ma J, Park S, Inoki K, Weisman L, Saltiel A. Phosphatidylinositol 3,5-bisphosphate plays a role in the activation and subcellular localization of mechanistic target of rapamycin 1. Mol Biol Cell. 2012;23:2955-62 pubmed publisher
    ..Furthermore, the mTORC1 component Raptor directly interacts with PI(3,5)P(2). Together these results suggest that PI(3,5)P(2) is an essential mTORC1 regulator that defines the localization of the complex. ..
  50. Kim D, Sarbassov D, Ali S, Latek R, Guntur K, Erdjument Bromage H, et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell. 2003;11:895-904 pubmed
    b>mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors...
  51. Gingras A, Raught B, Gygi S, Niedzwiecka A, Miron M, Burley S, et al. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 2001;15:2852-64 pubmed
    ..Finally, we show that phosphorylation of Ser 65 and Thr 70 alone is insufficient to block binding to eIF4E, indicating that a combination of phosphorylation events is necessary to dissociate 4E-BP1 from eIF4E. ..
  52. Leontieva O, Blagosklonny M. DNA damaging agents and p53 do not cause senescence in quiescent cells, while consecutive re-activation of mTOR is associated with conversion to senescence. Aging (Albany NY). 2010;2:924-35 pubmed
    When the cell cycle is arrested, growth-promoting pathways such as mTOR (Target of Rapamycin) drive cellular senescence, characterized by cellular hyper-activation, hypertrophy and permanent loss of the proliferative potential...
  53. Venkatesan A, Dehnhardt C, Delos Santos E, Chen Z, Dos Santos O, Ayral Kaloustian S, et al. Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J Med Chem. 2010;53:2636-45 pubmed publisher
    ..of bis(morpholino-1,3,5-triazine) derivatives were prepared and optimized to provide the highly efficacious PI3K/mTOR inhibitor 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)..
  54. Chen C, Jeon S, Bhaskar P, Nogueira V, Sundararajan D, Tonic I, et al. FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Dev Cell. 2010;18:592-604 pubmed publisher
    ..Here, we unraveled regulatory circuits underlying the interplay between Akt, FoxO, and mTOR. Activated FoxO1 inhibits mTORC1 by TSC2-dependent and TSC2-independent mechanisms...
  55. Dey N, Das F, Ghosh Choudhury N, Mandal C, Parekh D, Block K, et al. microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion. PLoS ONE. 2012;7:e37366 pubmed publisher
    ..Our results uncover a layer of post-transcriptional regulation of PTEN by transcriptional activation of miR-21 to force the canonical oncogenic Akt/TORC1 signaling conduit to drive renal cancer cell proliferation and invasion. ..
  56. Wang Y, Bai Y, Qin L, Zhang P, Yi T, Teesdale S, et al. Interferon-gamma induces human vascular smooth muscle cell proliferation and intimal expansion by phosphatidylinositol 3-kinase dependent mammalian target of rapamycin raptor complex 1 activation. Circ Res. 2007;101:560-9 pubmed
    ..Signaling by the mammalian target of rapamycin raptor complex, known as mTORC1, is associated with cell growth and is active within arteriosclerotic ..
  57. Hirashima K, Baba Y, Watanabe M, Karashima R, Sato N, Imamura Y, et al. Phosphorylated mTOR expression is associated with poor prognosis for patients with esophageal squamous cell carcinoma. Ann Surg Oncol. 2010;17:2486-93 pubmed publisher
    The mammalian target of rapamycin (mTOR) plays central roles in the regulation of cell growth and proliferation by monitoring nutrient availability, cellular energy level, oxygen level, and mitogenic signals...
  58. Han J, Jeong S, Park M, Kim G, Kwon N, Kim H, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149:410-24 pubmed publisher
    Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase, which regulates protein translation, cell size, and autophagy...
  59. Urano J, Sato T, Matsuo T, Otsubo Y, Yamamoto M, Tamanoi F. Point mutations in TOR confer Rheb-independent growth in fission yeast and nutrient-independent mammalian TOR signaling in mammalian cells. Proc Natl Acad Sci U S A. 2007;104:3514-9 pubmed
    ..In mammalian systems, we find that mammalian target of rapamycin (mTOR) carrying analogous mutations (L1460P or E2419K), although sensitive to rapamycin, exhibits ..
  60. García Martínez J, Alessi D. mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). Biochem J. 2008;416:375-85 pubmed publisher
    ..Recent work has established that mTORC1 [mTOR (mammalian target of rapamycin) complex 1] phosphorylates the hydrophobic motif of S6K (S6 kinase), whereas mTORC2 (mTOR complex 2) ..
  61. Reddy P, Legault H, Sypek J, Collins M, Goad E, Goldman S, et al. Mapping similarities in mTOR pathway perturbations in mouse lupus nephritis models and human lupus nephritis. Arthritis Res Ther. 2008;10:R127 pubmed publisher
    Treatment with sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to be efficacious in the MRL/lpr and NZB x NZW F1 mouse models of lupus nephritis, indicating a critical role for the mTOR pathway in both models...
  62. Hsu P, Kang S, Rameseder J, Zhang Y, Ottina K, Lim D, et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science. 2011;332:1317-22 pubmed publisher
    The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled by mTOR, few substrates are known...
  63. Cao Q, Ju X, Li P, Meng X, Shao P, Cai H, et al. A functional variant in the MTOR promoter modulates its expression and is associated with renal cell cancer risk. PLoS ONE. 2012;7:e50302 pubmed publisher
    The mTOR signaling pathway plays a crucial role in the carcinogenesis of renal cell cancer (RCC). We sought to investigate the influence of genetic variations in the mTOR pathway-related genes on the risk of RCC...
  64. Hoang B, Benavides A, Shi Y, Yang Y, Frost P, Gera J, et al. The PP242 mammalian target of rapamycin (mTOR) inhibitor activates extracellular signal-regulated kinase (ERK) in multiple myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic translation initiation factor 4E (eIF-4E)/RAF pathway and . J Biol Chem. 2012;287:21796-805 pubmed publisher
    Activation of PI3-K-AKT and ERK pathways is a complication of mTOR inhibitor therapy. Newer mTOR inhibitors (like pp242) can overcome feedback activation of AKT in multiple myeloma (MM) cells...
  65. McMahon L, Yue W, Santen R, Lawrence J. Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity both in cells and in vitro by promoting dissociation of the mTOR-raptor complex. Mol Endocrinol. 2005;19:175-83 pubmed
    The mammalian target of rapamycin (mTOR) functions with raptor and mLST8 in a signaling complex that controls rates of cell growth and proliferation...
  66. Kantidakis T, Ramsbottom B, Birch J, Dowding S, White R. mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. Proc Natl Acad Sci U S A. 2010;107:11823-8 pubmed publisher
    Synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III is regulated by the mTOR pathway in mammalian cells. The mTOR kinase localizes to tRNA and 5S rRNA genes, providing an opportunity for direct control...
  67. Buerger C, DeVries B, Stambolic V. Localization of Rheb to the endomembrane is critical for its signaling function. Biochem Biophys Res Commun. 2006;344:869-80 pubmed
    Rheb, a small GTPase, has emerged as a key molecular switch that directly regulates the activity of the mammalian target of rapamycin (mTOR)...
  68. Sahin F, Kannangai R, Adegbola O, Wang J, Su G, Torbenson M. mTOR and P70 S6 kinase expression in primary liver neoplasms. Clin Cancer Res. 2004;10:8421-5 pubmed
    b>mTOR and P70 S6 kinase (S6K) play a key role in regulating protein translation...
  69. Shor B, Zhang W, Toral Barza L, Lucas J, Abraham R, Gibbons J, et al. A new pharmacologic action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis. Cancer Res. 2008;68:2934-43 pubmed publisher
    The mammalian target of rapamycin (mTOR) inhibitor CCI-779 (temsirolimus) is a recently Food and Drug Administration-approved anticancer drug with efficacy in certain solid tumors and hematologic malignancies...
  70. Miyazawa M, Yasuda M, Fujita M, Kajiwara H, Hirabayashi K, Takekoshi S, et al. Therapeutic strategy targeting the mTOR-HIF-1alpha-VEGF pathway in ovarian clear cell adenocarcinoma. Pathol Int. 2009;59:19-27 pubmed publisher
    ..Thus, inhibition of the mammalian target of rapamycin (mTOR) pathway including HIF-1alpha is expected to play a major role in suppression of tumor cell ..
  71. Kaizuka T, Hara T, Oshiro N, Kikkawa U, Yonezawa K, Takehana K, et al. Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly. J Biol Chem. 2010;285:20109-16 pubmed publisher
    b>Mammalian target of rapamycin (mTOR) is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family and is a major regulator of translation, cell growth, and autophagy...
  72. Fang Y, Vilella Bach M, Bachmann R, Flanigan A, Chen J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science. 2001;294:1942-5 pubmed
    The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by mediating the mitogen- and nutrient-dependent signal transduction that regulates messenger RNA translation...
  73. Darb Esfahani S, Faggad A, Noske A, Weichert W, Buckendahl A, Müller B, et al. Phospho-mTOR and phospho-4EBP1 in endometrial adenocarcinoma: association with stage and grade in vivo and link with response to rapamycin treatment in vitro. J Cancer Res Clin Oncol. 2009;135:933-41 pubmed publisher
    ..due to a frequent activation of PI3 K/AKT has been proposed as a candidate neoplasm for the treatment with mTOR inhibitors. Yet, data on the expression of mTOR cascade components in endometrial cancer are lacking...
  74. Dowling R, Topisirovic I, Fonseca B, Sonenberg N. Dissecting the role of mTOR: lessons from mTOR inhibitors. Biochim Biophys Acta. 2010;1804:433-9 pubmed publisher
    ..Consistent with its role in cell proliferation, the mTOR pathway is frequently hyperactivated in a number of human malignancies and is thus considered to be an attractive ..
  75. Boulbes D, Chen C, Shaikenov T, Agarwal N, Peterson T, Addona T, et al. Rictor phosphorylation on the Thr-1135 site does not require mammalian target of rapamycin complex 2. Mol Cancer Res. 2010;8:896-906 pubmed publisher
    ..The PI3K-dependent signaling kinase complex defined as mammalian target of rapamycin complex 2 (mTORC2) functions as a regulatory Ser-473 kinase of Akt...
  76. Johnson S, Rabinovitch P, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature. 2013;493:338-45 pubmed publisher
    ..target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR)...
  77. Fingar D, Salama S, Tsou C, Harlow E, Blenis J. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 2002;16:1472-87 pubmed
    ..cell cycle progression are separable processes in mammalian cells and that growth to appropriate cell size requires mTOR- and PI3K-dependent signals...
  78. Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, et al. 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. 2003;278:15461-4 pubmed
    The mammalian target of rapamycin (mTOR) controls multiple cellular functions in response to amino acids and growth factors, in part by regulating the phosphorylation of p70 S6 kinase (p70S6k) and eukaryotic initiation factor 4E-binding ..
  79. Sancak Y, Thoreen C, Peterson T, Lindquist R, Kang S, Spooner E, et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell. 2007;25:903-15 pubmed
    ..We propose that the relative strengths of the rheb- and PRAS40-mediated inputs to mTORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both. ..
  80. Choo A, Yoon S, Kim S, Roux P, Blenis J. Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation. Proc Natl Acad Sci U S A. 2008;105:17414-9 pubmed publisher
    ..This reemerged 4E-BP1 phosphorylation is rapamycin-resistant but still requires mTOR, Raptor, and mTORC1's activity...
  81. Murayama T, Inokuchi M, Takagi Y, Yamada H, Kojima K, Kumagai J, et al. Relation between outcomes and localisation of p-mTOR expression in gastric cancer. Br J Cancer. 2009;100:782-8 pubmed publisher
    The mammalian target of rapamycin (mTOR), a Ser/Thr protein kinase that mediates intracellular signalling related to cell growth, proliferation, and differentiation, has received considerable interest as a possible target for cancer ..