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. Sebestyen A, Sticz T, Márk A, Hajdu M, Timár B, Nemes K, et al. Activity and complexes of mTOR in diffuse large B-cell lymphomas--a tissue microarray study. Mod Pathol. 2012;25:1623-8 pubmed publisher
    ..Targeting mTOR (mammalian target of rapamycin) offers a new approach to improve the treatment...
  7. Lee D, Kuo H, Chen C, Hsu J, Chou C, Wei Y, et al. IKK beta suppression of TSC1 links inflammation and tumor angiogenesis via the mTOR pathway. Cell. 2007;130:440-55 pubmed
    ..The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis...
  8. Dreyer H, Drummond M, Pennings B, Fujita S, Glynn E, Chinkes D, et al. Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. 2008;294:E392-400 pubmed
    ..and ingestion of essential amino acids with carbohydrate (EAA+CHO) can independently stimulate mammalian target of rapamycin (mTOR) signaling and muscle protein synthesis in humans...
  9. Misra U, Pizzo S. Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex. J Cell Biochem. 2012;113:1488-500 pubmed publisher
    ..We measured mTORC2-dependent Akt phosphorylation at S473 in immunoprecipitates of mTOR or Rictor from 1-LN cells...

More Information

Publications250 found, 100 shown here

  1. Gately K, Al Alao B, T Dhillon -, Mauri F, Cuffe S, Seckl M, et al. Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: a verification study. Lung Cancer. 2012;75:217-22 pubmed publisher
    A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC...
  2. Munk R, Ghosh P, Ghosh M, Saito T, Xu M, Carter A, et al. Involvement of mTOR in CXCL12 mediated T cell signaling and migration. PLoS ONE. 2011;6:e24667 pubmed publisher
    ..b>Mammalian target of rapamycin (mTOR) is a serine-threonine kinase that modulates different cellular processes, such as metabolism, ..
  3. Chung J, Bachelder R, Lipscomb E, Shaw L, Mercurio A. Integrin (alpha 6 beta 4) regulation of eIF-4E activity and VEGF translation: a survival mechanism for carcinoma cells. J Cell Biol. 2002;158:165-74 pubmed
    ..the ability of this integrin to activate the PI-3K-Akt pathway and, consequently, the rapamycin-sensitive kinase mTOR that can phosphorylate 4E-BP1...
  4. Grabinski N, Ewald F, Hofmann B, Staufer K, Schumacher U, Nashan B, et al. Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells. Mol Cancer. 2012;11:85 pubmed publisher
    Due to the frequent dysregulation of the PI3K/AKT/mTOR signaling pathway, mTOR represents a suitable therapeutic target in hepatocellular carcinoma (HCC)...
  5. Zinzalla V, Stracka D, Oppliger W, Hall M. Activation of mTORC2 by association with the ribosome. Cell. 2011;144:757-68 pubmed publisher
    ..As ribosome content determines growth capacity of a cell, this mechanism of TORC2 regulation ensures that TORC2 is active only in growing cells. ..
  6. Gingras A, Gygi S, Raught B, Polakiewicz R, Abraham R, Hoekstra M, et al. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev. 1999;13:1422-37 pubmed
    ..The PI3-kinase/Akt pathway and the kinase FRAP/mTOR signal to 4E-BP1. FRAP/mTOR has been reported to phosphorylate 4E-BP1 directly in vitro...
  7. Vander Haar E, Lee S, Bandhakavi S, Griffin T, Kim D. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol. 2007;9:316-23 pubmed
    ..and cell growth by activation of the protein kinases Akt (also known as protein kinase B, PKB) and mammalian target of rapamycin (mTOR)...
  8. Loi S, Haibe Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, et al. PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer. Proc Natl Acad Sci U S A. 2010;107:10208-13 pubmed publisher
    ..and hence these lesions have been hypothesized to render tumors highly sensitive to therapeutic PI3K/mTOR inhibition...
  9. Tzatsos A, Kandror K. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol. 2006;26:63-76 pubmed
    ..that nutrients suppress phosphatidylinositol 3 (PI3)-kinase/Akt signaling via Raptor-dependent mTOR (mammalian target of rapamycin)-mediated phosphorylation of insulin receptor substrate 1 (IRS-1)...
  10. Regimbald Dumas Y, Fregeau M, Guillemette G. Mammalian target of rapamycin (mTOR) phosphorylates inositol 1,4,5-trisphosphate receptor type 2 and increases its Ca(2+) release activity. Cell Signal. 2011;23:71-9 pubmed publisher
    ..Here we report that mTOR, a point of convergence for signals from mitogenic growth factors, nutrients and cellular energy levels, ..
  11. Sun Y, Fang Y, Yoon M, Zhang C, Roccio M, Zwartkruis F, et al. Phospholipase D1 is an effector of Rheb in the mTOR pathway. Proc Natl Acad Sci U S A. 2008;105:8286-91 pubmed publisher
    The mammalian target of rapamycin (mTOR) assembles a signaling network essential for the regulation of cell growth, which has emerged as a major target of anticancer therapies...
  12. Kumar V, Pandey P, Sabatini D, Kumar M, Majumder P, Bharti A, et al. Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of translation. EMBO J. 2000;19:1087-97 pubmed
    ..The rapamycin and FK506-binding protein (FKBP)-target 1 (RAFT1, also known as FRAP) is a mammalian homolog of the Saccharomyces cerevisiae target of rapamycin proteins (mTOR) ..
  13. Sabers C, Martin M, Brunn G, Williams J, Dumont F, Wiederrecht G, et al. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem. 1995;270:815-22 pubmed
    ..S-transferase (GST)-FKBP12-rapamycin affinity matrix to isolate putative mammalian targets of rapamycin (mTOR) from tissue extracts...
  14. Hietakangas V, Cohen S. TOR complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells. BMC Cancer. 2008;8:282 pubmed publisher
    ..This study provides further evidence that inhibition of TORC2 activity might be a useful strategy to inhibit proliferation of tumor cells and subsequent tumor growth. ..
  15. Drenan R, Liu X, Bertram P, Zheng X. FKBP12-rapamycin-associated protein or mammalian target of rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi apparatus. J Biol Chem. 2004;279:772-8 pubmed
    FKBP12-rapamycin-associated protein (FRAP) or mammalian target of rapamycin (mTOR) and its effector proteins form a critical signaling pathway that regulates eukaryotic cell growth and proliferation...
  16. Smith E, Proud C. cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner. EMBO J. 2008;27:1005-16 pubmed publisher
    ..starvation decreases cdc2's activity against eEF2K, whereas loss of TSC2 (a negative regulator of mammalian target of rapamycin complex 1(mTORC1)) increases it...
  17. Cui L, Zhou H, Zhao H, Zhou Y, Xu R, Xu X, et al. MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma. BMC Cancer. 2012;12:546 pubmed publisher
    ..In addition, we also fond that mammalian target of rapamycin (mTOR) was a direct target of miR-99a in RCC cells...
  18. Harhaji Trajkovic L, Vilimanovich U, Kravic Stevovic T, Bumbasirevic V, Trajkovic V. AMPK-mediated autophagy inhibits apoptosis in cisplatin-treated tumour cells. J Cell Mol Med. 2009;13:3644-54 pubmed publisher
    ..of adenosine monophosphate-activated protein kinase (AMPK) and concomitant down-regulation of mammalian target of rapamycin (mTOR)-mediated phosphorylation of p70S6 kinase...
  19. Narita M, Young A, Arakawa S, Samarajiwa S, Nakashima T, Yoshida S, et al. Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science. 2011;332:966-70 pubmed publisher
    Protein synthesis and autophagic degradation are regulated in an opposite manner by mammalian target of rapamycin (mTOR), whereas under certain conditions it would be beneficial if they occurred in unison to handle rapid protein turnover...
  20. Martin J, Masri J, Bernath A, Nishimura R, Gera J. Hsp70 associates with Rictor and is required for mTORC2 formation and activity. Biochem Biophys Res Commun. 2008;372:578-83 pubmed publisher
    mTORC2 is a multiprotein kinase composed of mTOR, mLST8, PRR5, mSIN1 and Rictor. The complex is insensitive to rapamycin and has demonstrated functions controlling cell growth, motility, invasion and cytoskeletal assembly...
  21. Carracedo A, Ma L, Teruya Feldstein J, Rojo F, Salmena L, Alimonti A, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest. 2008;118:3065-74 pubmed publisher
    Numerous studies have established a causal link between aberrant mammalian target of rapamycin (mTOR) activation and tumorigenesis, indicating that mTOR inhibition may have therapeutic potential...
  22. Ingels A, Zhao H, Thong A, Saar M, Valta M, Nolley R, et al. Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts. Int J Cancer. 2014;134:2322-9 pubmed publisher
    b>mTOR is a rational target in renal cell carcinoma (RCC) because of its role in disease progression...
  23. Fonseca B, Smith E, Lee V, MacKintosh C, Proud C. PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex. J Biol Chem. 2007;282:24514-24 pubmed
    Signaling through the mammalian target of rapamycin complex 1 (mTORC1) is positively regulated by amino acids and insulin. PRAS40 associates with mTORC1 (which contains raptor) but not mTORC2...
  24. Lu Z, Shvartsman M, Lee A, Shao J, Murray M, Kladney R, et al. Mammalian target of rapamycin activator RHEB is frequently overexpressed in human carcinomas and is critical and sufficient for skin epithelial carcinogenesis. Cancer Res. 2010;70:3287-98 pubmed publisher
    ..Our findings offer direct evidence that RHEB facilitates multistage carcinogenesis through induction of multiple oncogenic mechanisms, perhaps contributing to the poor prognosis of patients with cancers overexpressing RHEB. ..
  25. Smith E, Finn S, Tee A, Browne G, Proud C. The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J Biol Chem. 2005;280:18717-27 pubmed
    Amino acids positively regulate signaling through the mammalian target of rapamycin (mTOR). Recent work demonstrated the importance of the tuberous sclerosis protein TSC2 for regulation of mTOR by insulin...
  26. Bitanihirwe B, Meerang M, Friess M, Soltermann A, Frischknecht L, Thies S, et al. PI3K/mTOR signaling in mesothelioma patients treated with induction chemotherapy followed by extrapleural pneumonectomy. J Thorac Oncol. 2014;9:239-47 pubmed publisher
    The prognostic significance of activity biomarkers within the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway was assessed in two independent cohorts of malignant pleural mesothelioma (MPM) ..
  27. Thomas G, Tran C, Mellinghoff I, Welsbie D, Chan E, Fueger B, et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med. 2006;12:122-7 pubmed
    Inhibitors of the kinase mammalian target of rapamycin (mTOR) have shown sporadic activity in cancer trials, leading to confusion about the appropriate clinical setting for their use...
  28. Peterson T, Laplante M, Thoreen C, Sancak Y, Kang S, Kuehl W, et al. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009;137:873-86 pubmed publisher
    The mTORC1 and mTORC2 pathways regulate cell growth, proliferation, and survival. We identify DEPTOR as an mTOR-interacting protein whose expression is negatively regulated by mTORC1 and mTORC2...
  29. Desai B, Myers B, Schreiber S. FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc Natl Acad Sci U S A. 2002;99:4319-24 pubmed
    FKBP12-rapamycin associated protein (FRAP, also known as mTOR or RAFT) is the founding member of the phosphatidylinositol kinase-related kinase family and functions as a sensor of physiological signals that regulate cell growth...
  30. Pignochino Y, Dell Aglio C, Basiricò M, Capozzi F, Soster M, Marchio S, et al. The Combination of Sorafenib and Everolimus Abrogates mTORC1 and mTORC2 upregulation in osteosarcoma preclinical models. Clin Cancer Res. 2013;19:2117-31 pubmed publisher
    ..Immunoprecipitation, Western blotting, and immunohistochemistry were used to analyze the mTOR pathway [mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)]...
  31. 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)...
  32. 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
  33. 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-..
  34. 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...
  35. 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.
  36. 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 ...
  37. 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...
  38. 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...
  39. Chen Y, Rodrik V, Foster D. Alternative phospholipase D/mTOR survival signal in human breast cancer cells. Oncogene. 2005;24:672-9 pubmed
    ..One of the targets of PLD signaling is mTOR (mammalian target of rapamycin), a critical regulator of cell cycle progression and cell growth...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. Sekulic A, Hudson C, Homme J, Yin P, Otterness D, Karnitz L, et al. A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 2000;60:3504-13 pubmed
    ..agent rapamycin inhibits cell growth by interfering with the signaling functions of the mammalian target of rapamycin (mTOR)...
  45. 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...
  46. 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...
  47. 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 ..
  48. Zhang X, Shu L, Hosoi H, Murti K, Houghton P. Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture. J Biol Chem. 2002;277:28127-34 pubmed
    b>Mammalian target of rapamycin (mTOR) controls initiation of translation through regulation of ribosomal p70S6 kinase (S6K1) and eukaryotic translation initiation factor-4E (eIF4E) binding protein (4E-BP)...
  49. 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...
  50. Mendoza M, Er E, Blenis J. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation. Trends Biochem Sci. 2011;36:320-8 pubmed publisher
    The Ras-extracellular signal-regulated kinase (Ras-ERK) and phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) signaling pathways are the chief mechanisms for controlling cell survival, differentiation, proliferation,..
  51. 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...
  52. 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...
  53. 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...
  54. 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...
  55. Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007;104:16158-63 pubmed
    ..Notably, signaling of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR), signal transduction and activator of transcription (STAT3), and phosphatase and tensin homolog ..
  56. 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...
  57. 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...
  58. 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...
  59. 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...
  60. 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)...
  61. 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 ..
  62. 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...
  63. 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...
  64. 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...
  65. 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...
  66. 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 ..
  67. 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. ..
  68. 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...
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    ..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...
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    ..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...
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    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...
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    ..A key effector of Akt-induced signaling is the regulatory protein mTOR (mammalian target of rapamycin)...
  74. 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...
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    Activated mTOR was implicated to play a role in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the mechanism of activated mTOR/Complex1(mTORC1) signaling pathway in NPC development has not been well established...
  76. 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...
  77. 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...
  78. 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...
  79. 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...
  80. 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...
  81. Yokogami K, Wakisaka S, Avruch J, Reeves S. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr Biol. 2000;10:47-50 pubmed
    ..protein kinase (MAPK), phosphatidylinositol 3-kinase (PI 3-kinase) and mammalian target of rapamydn (mTOR)-p70 S6 kinase ...
  82. Faried L, Faried A, Kanuma T, Sano T, Nakazato T, Tamura T, et al. Predictive and prognostic role of activated mammalian target of rapamycin in cervical cancer treated with cisplatin-based neoadjuvant chemotherapy. Oncol Rep. 2006;16:57-63 pubmed
    The present study was designed to clarify the expression and prognostic significance of activated Akt and mTOR in cervical cancer and their correlation with response to neoadjuvant chemotherapy (NAC)...
  83. 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)...
  84. 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.
  85. 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...
  86. 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...
  87. 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)...
  88. 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...
  89. 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...
  90. 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 ..
  91. 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. ..
  92. 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...