Rptor

Summary

Gene Symbol: Rptor
Description: regulatory associated protein of MTOR, complex 1
Alias: 4932417H02Rik, Rap, Raptor, mKIAA1303, regulatory-associated protein of mTOR, p150 target of rapamycin (TOR)-scaffold protein
Species: mouse
Products:     Rptor

Top Publications

  1. Kalaitzidis D, Sykes S, Wang Z, Punt N, Tang Y, Ragu C, et al. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell. 2012;11:429-39 pubmed publisher
    ..We deleted the mTORC1 component, regulatory-associated protein of mTOR (Raptor), in mouse HSCs and its loss causes a nonlethal phenotype characterized by pancytopenia, splenomegaly, and the ..
  2. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002;110:177-89 pubmed
    ..b>Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha...
  3. Bentzinger C, Romanino K, Cloëtta D, Lin S, Mascarenhas J, Oliveri F, et al. Skeletal muscle-specific ablation of raptor, but not of rictor, causes metabolic changes and results in muscle dystrophy. Cell Metab. 2008;8:411-24 pubmed publisher
    ..Here we show that the mTORC1 component raptor is critical for muscle function and prolonged survival...
  4. 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
    ..mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the ..
  5. Cunningham J, Rodgers J, Arlow D, Vazquez F, Mootha V, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007;450:736-40 pubmed
    ..Moreover, mTOR and raptor interacted with YY1, and inhibition of mTOR resulted in a failure of YY1 to interact with and be coactivated by ..
  6. Sengupta S, Peterson T, Laplante M, Oh S, Sabatini D. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature. 2010;468:1100-4 pubmed publisher
    ..The loss of raptor (regulatory associated protein of mTOR, complex 1) an essential mTORC1 component, has the opposite effects...
  7. Zhang H, Huang J, Düvel K, Boback B, Wu S, Squillace R, et al. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS ONE. 2009;4:e6189 pubmed publisher
    ..Therefore, the TSC1-TSC2 complex regulates the differentiation of mesenchymal cell lineages, at least in part, through its control of mTORC1 activity and PPARgamma expression. ..
  8. Laplante M, Sabatini D. mTOR signaling in growth control and disease. Cell. 2012;149:274-93 pubmed publisher
    ..Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation. ..
  9. Patursky Polischuk I, Stolovich Rain M, Hausner Hanochi M, Kasir J, Cybulski N, Avruch J, et al. The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner. Mol Cell Biol. 2009;29:640-9 pubmed publisher
    ..However, knockout of the raptor or rictor gene has only a slight effect on the translation efficiency of these mRNAs, implying that mTOR exerts ..

More Information

Publications93

  1. Gwinn D, Shackelford D, Egan D, Mihaylova M, Mery A, Vasquez D, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008;30:214-26 pubmed publisher
    ..We report here that AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor...
  2. Hoshii T, Tadokoro Y, Naka K, Ooshio T, Muraguchi T, Sugiyama N, et al. mTORC1 is essential for leukemia propagation but not stem cell self-renewal. J Clin Invest. 2012;122:2114-29 pubmed publisher
    ..We investigated the role of mTORC1 in mouse hematopoiesis using a mouse model of conditional deletion of Raptor, an essential component of mTORC1...
  3. Shah O, Hunter T. Turnover of the active fraction of IRS1 involves raptor-mTOR- and S6K1-dependent serine phosphorylation in cell culture models of tuberous sclerosis. Mol Cell Biol. 2006;26:6425-34 pubmed
    The TSC1-TSC2/Rheb/Raptor-mTOR/S6K1 cell growth cassette has recently been shown to regulate cell autonomous insulin and insulin-like growth factor I (IGF-I) sensitivity by transducing a negative feedback signal that targets insulin ..
  4. Polak P, Cybulski N, Feige J, Auwerx J, Ruegg M, Hall M. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 2008;8:399-410 pubmed publisher
    b>raptor is a specific and essential component of mammalian TOR complex 1 (mTORC1), a key regulator of cell growth and metabolism...
  5. Guertin D, Stevens D, Thoreen C, Burds A, Kalaany N, Moffat J, et al. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006;11:859-71 pubmed
    ..mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively...
  6. 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 identify PRAS40 as a raptor-interacting protein that binds to mTORC1 in insulin-deprived cells and whose in vitro interaction with mTORC1 is ..
  7. Huang B, Wang W, Li Q, Wang Z, Yan B, Zhang Z, et al. Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone. Nat Commun. 2016;7:13885 pubmed publisher
    ..These findings reveal the essential role of osteoblast-produced Cxcl9 in angiogenesis and osteogenesis in bone, and Cxcl9 can be targeted to elevate bone angiogenesis and prevent bone loss-related diseases. ..
  8. Cloëtta D, Thomanetz V, Baranek C, Lustenberger R, Lin S, Oliveri F, et al. Inactivation of mTORC1 in the developing brain causes microcephaly and affects gliogenesis. J Neurosci. 2013;33:7799-810 pubmed publisher
    ..In this study, we inactivated mTORC1 in mice by deleting the gene encoding raptor in the progenitors of the developing CNS. Mice are born but never feed and die within a few hours...
  9. Potter W, Basu T, O Riordan K, Kirchner A, Rutecki P, Burger C, et al. Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling. PLoS Biol. 2013;11:e1001627 pubmed publisher
    ..These findings highlight the potential of modulating the mGluR5-Erk pathway in a developmental stage-specific manner to treat TSC. ..
  10. Liu D, Bordicchia M, Zhang C, Fang H, Wei W, Li J, et al. Activation of mTORC1 is essential for ?-adrenergic stimulation of adipose browning. J Clin Invest. 2016;126:1704-16 pubmed publisher
    ..Mice with mTORC1 impairment, either through adipocyte-specific deletion of Raptor or pharmacologic rapamycin treatment, were refractory to the well-known ?AR-dependent increase of uncoupling ..
  11. Sampson L, Davis A, Grogg M, Zheng Y. mTOR disruption causes intestinal epithelial cell defects and intestinal atrophy postinjury in mice. FASEB J. 2016;30:1263-75 pubmed publisher
    ..We disrupted the genes mTOR, Rptor, Rictor, or both Rptor and Rictor in mouse ISCs, progenitors, and differentiated intestinal epithelial cells (IECs)..
  12. Rodgers J, King K, Brett J, Cromie M, Charville G, Maguire K, et al. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to G(Alert). Nature. 2014;510:393-6 pubmed publisher
  13. Wang M, Guo Y, Wang M, Zhou T, Xue Y, Du G, et al. The Glial Cell-Derived Neurotrophic Factor (GDNF)-responsive Phosphoprotein Landscape Identifies Raptor Phosphorylation Required for Spermatogonial Progenitor Cell Proliferation. Mol Cell Proteomics. 2017;16:982-997 pubmed publisher
    ..Significantly, we found that proliferation of SPCs requires phosphorylation of the mTORC1 component Raptor at Ser863 Tissue-specific deletion of Raptor in mouse germline cells results in impaired ..
  14. Chen W, Lu N, Ding Y, Wang Y, Chan L, Wang X, et al. Rapamycin-Resistant mTOR Activity Is Required for Sensory Axon Regeneration Induced by a Conditioning Lesion. Eneuro. 2016;3: pubmed publisher
    ..results from functions of mTOR complex 1 (mTORC1) or 2 (mTORC2), two distinct kinase complexes, we ablated either Raptor or Rictor in DRG neurons...
  15. Zhang Y, Xu S, Liang K, Li K, Zou Z, Yang C, et al. Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes. J Biol Chem. 2017;292:100-111 pubmed publisher
    ..Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller ..
  16. Sutton L, Caron M. Essential role of D1R in the regulation of mTOR complex1 signaling induced by cocaine. Neuropharmacology. 2015;99:610-9 pubmed publisher
    ..and that this increase in phosphorylated mTOR levels was also apparent when complexed with its binding partner Raptor. Furthermore, the increase in phosphorylated mTOR levels, as well as phosphorylated 4E-BP1 and S6K, downstream ..
  17. Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, et al. Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice. Am J Respir Cell Mol Biol. 2016;55:722-735 pubmed
    ..Specifically, inhibiting regulatory-associated protein of mechanistic target of rapamycin (RPTOR) in hyperoxia settings, as evidenced by wild-type mice treated with torin2 or mice administered (Rptor) silencing ..
  18. Xu X, Zhang Z, Su W, Zhang Y, Yu Y, Li Y, et al. Characterization of p70 S6 kinase 1 in early development of mouse embryos. Dev Dyn. 2009;238:3025-34 pubmed publisher
    ..Down-regulating mTOR and raptor reduced S6K1 phosphorylation at Thr389 in one-cell embryos...
  19. Kellersch B, Brocker T. Langerhans cell homeostasis in mice is dependent on mTORC1 but not mTORC2 function. Blood. 2013;121:298-307 pubmed publisher
    ..seeding of the epidermis with LCs is not affected, the lack of mTORC1 activity in DCs by conditional deletion of Raptor leads to a progressive loss of LCs in the skin of mice...
  20. Ohtani M, Hoshii T, Fujii H, Koyasu S, Hirao A, Matsuda S. Cutting edge: mTORC1 in intestinal CD11c+ CD11b+ dendritic cells regulates intestinal homeostasis by promoting IL-10 production. J Immunol. 2012;188:4736-40 pubmed publisher
    ..We therefore established mTORC1 signal-deficient mice lacking Raptor, an essential component of mTORC1 signal, specifically in DC lineage (referred to here as Raptor(DC-/-))...
  21. Chen J, Tu X, Esen E, Joeng K, Lin C, Arbeit J, et al. WNT7B promotes bone formation in part through mTORC1. PLoS Genet. 2014;10:e1004145 pubmed publisher
    ..WNT7B activated mTORC1 through PI3K-AKT signaling. Genetic disruption of mTORC1 signaling by deleting Raptor in the osteoblast lineage alleviated the WNT7B-induced high-bone-mass phenotype...
  22. Jiang M, Fu X, Yang H, Long F, Chen J. mTORC1 Signaling Promotes Limb Bud Cell Growth and Chondrogenesis. J Cell Biochem. 2017;118:748-753 pubmed publisher
    ..In this study, we first deleted Raptor, a unique and essential component of mTORC1, in prechondrogenic limb mesenchymal cells...
  23. Chen L, Wu M, Zhu F, Kai J, Dong J, Wu X, et al. Neural Progenitor Cells Rptor Ablation Impairs Development but Benefits to Seizure-Induced Behavioral Abnormalities. CNS Neurosci Ther. 2016;22:1000-1008 pubmed publisher
    ..The present work was designed to explore the contribution of raptor protein to the development of epilepsy and comorbidities...
  24. Tang F, Zhang P, Ye P, Lazarski C, Wu Q, Bergin I, et al. A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice. elife. 2017;6: pubmed publisher
    ..Our data unveil a novel leukocyte population and an unrecognized role of Raptor/mTORC1 in innate immune tolerance.
  25. Rosner M, Hengstschlager M. Cytoplasmic and nuclear distribution of the protein complexes mTORC1 and mTORC2: rapamycin triggers dephosphorylation and delocalization of the mTORC2 components rictor and sin1. Hum Mol Genet. 2008;17:2934-48 pubmed publisher
    The mammalian target of rapamycin (mTOR) is part of two distinct complexes, mTORC1, containing raptor and mLST8, and mTORC2, containing rictor, mLST8 and sin1...
  26. Pollard H, Willett M, Morley S. mTOR kinase-dependent, but raptor-independent regulation of downstream signaling is important for cell cycle exit and myogenic differentiation. Cell Cycle. 2014;13:2517-25 pubmed publisher
    ..as cells exit the cell cycle, using inhibitors to target mTOR kinase and siRNAs to ablate the expression of raptor and rictor...
  27. Chakrabarti P, English T, Shi J, Smas C, Kandror K. Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage. Diabetes. 2010;59:775-81 pubmed publisher
    ..Inhibition of mTORC1 signaling by rapamycin or by knockdown of raptor stimulates lipolysis primarily via activation of ATGL expression...
  28. Guertin D, Stevens D, Saitoh M, Kinkel S, Crosby K, Sheen J, et al. mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell. 2009;15:148-59 pubmed publisher
    ..The selective requirement for mTORC2 in tumor development suggests that mTORC2 inhibitors may be of substantial clinical utility. ..
  29. Huynh H, Wei W, Wan Y. mTOR Inhibition Subdues Milk Disorder Caused by Maternal VLDLR Loss. Cell Rep. 2017;19:2014-2025 pubmed publisher
    ..Our studies uncover functions of VLDLR and mTORC1 in lactation and osteoclastogenesis, illuminating key mechanisms and therapeutic insights for bone and metabolic diseases. ..
  30. Kim K, Qiang L, Hayden M, Sparling D, Purcell N, Pajvani U. mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2. Nat Commun. 2016;7:10255 pubmed publisher
    Mechanistic target of rapamycin complex 1 (mTORC1), defined by the presence of Raptor, is an evolutionarily conserved and nutrient-sensitive regulator of cellular growth and other metabolic processes...
  31. Xiao M, Wang Y, Tao C, Wang Z, Yang J, Chen Z, et al. Osteoblasts support megakaryopoiesis through production of interleukin-9. Blood. 2017;129:3196-3209 pubmed publisher
    ..These data indicate that IL-9 is an essential regulator of megakaryopoiesis and a promising therapeutic agent for treatment of thrombocytopenia such as CIT. ..
  32. Linares J, Duran A, Yajima T, Pasparakis M, Moscat J, Diaz Meco M. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol Cell. 2013;51:283-96 pubmed publisher
    ..The signaling adaptor p62 binds raptor, and integral component of the mTORC1 pathway...
  33. Shende P, Plaisance I, Morandi C, Pellieux C, Berthonneche C, Zorzato F, et al. Cardiac raptor ablation impairs adaptive hypertrophy, alters metabolic gene expression, and causes heart failure in mice. Circulation. 2011;123:1073-82 pubmed publisher
    ..We generated mice with deficient myocardial mTORC1 activity by targeted ablation of raptor, which encodes an essential component of mTORC1, during adulthood...
  34. Li D, Wang C, Yao Y, Chen L, Liu G, Zhang R, et al. mTORC1 pathway disruption ameliorates brain inflammation following stroke via a shift in microglia phenotype from M1 type to M2 type. FASEB J. 2016;30:3388-3399 pubmed
    ..For that purpose, we generated mice deficient in the regulatory associated protein of mTOR (Raptor) in microglia, whose mTORC1 signaling was blocked, by crossing Raptor loxed (Raptor..
  35. Liemburg Apers D, Wagenaars J, Smeitink J, Willems P, Koopman W. Acute stimulation of glucose influx upon mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR-RAPTOR. J Cell Sci. 2016;129:4411-4423 pubmed
    ..Stimulation of glucose uptake was greatly reduced by chemical inhibition of Sirt2 or mTOR-RAPTOR. We propose that mitochondrial dysfunction triggers LKB1-mediated AMPK activation, which stimulates Sirt2 ..
  36. Hu J, Du W, Shelton S, Oldham M, DiPersio C, Klein O. An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell. 2017;21:91-106.e6 pubmed publisher
    ..This leads to Rheb expression and potentiates mTOR signaling to drive the proliferation of TA cells. These findings thus reveal a YAP/TAZ signaling mechanism that coordinates stem cell expansion and differentiation during organ renewal. ..
  37. Dai Q, Xie F, Han Y, Ma X, Zhou S, Jiang L, et al. Inactivation of Regulatory-associated Protein of mTOR (Raptor)/Mammalian Target of Rapamycin Complex 1 (mTORC1) Signaling in Osteoclasts Increases Bone Mass by Inhibiting Osteoclast Differentiation in Mice. J Biol Chem. 2017;292:196-204 pubmed publisher
    ..In this study, we showed that deletion of regulatory-associated protein of mTOR (Raptor) in osteoclasts led to an increase in bone mass with decreased bone resorption...
  38. Xiong M, Zhu Z, Tian S, Zhu R, Bai S, Fu K, et al. Conditional ablation of Raptor in the male germline causes infertility due to meiotic arrest and impaired inactivation of sex chromosomes. FASEB J. 2017;31:3934-3949 pubmed publisher
    ..Here, we inactivate the core component, Raptor, to show that mTORC1 function is critical for male meiosis and the inactivation of sex chromosomes...
  39. Mills J, Hippo Y, Robert F, Chen S, Malina A, Lin C, et al. mTORC1 promotes survival through translational control of Mcl-1. Proc Natl Acad Sci U S A. 2008;105:10853-8 pubmed publisher
    ..Our results indicate that the extent by which rapamycin can modulate expression of Mcl-1 is an important feature of the rapamycin response. ..
  40. Koketsu Y, Sakoda H, Fujishiro M, Kushiyama A, Fukushima Y, Ono H, et al. Hepatic overexpression of a dominant negative form of raptor enhances Akt phosphorylation and restores insulin sensitivity in K/KAy mice. Am J Physiol Endocrinol Metab. 2008;294:E719-25 pubmed publisher
    ..In this study, to investigate the effect of mTOR/raptor on insulin signaling and metabolism in K/KAy mice with genetic obesity-associated insulin resistance, a dominant ..
  41. Dey N, Das F, Mariappan M, Mandal C, Ghosh Choudhury N, Kasinath B, et al. MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes. J Biol Chem. 2011;286:25586-603 pubmed publisher
    ..Thus, our results identify a previously unrecognized function of miR-21 that is the reciprocal regulation of PTEN levels and Akt/TORC1 activity that mediate critical pathologic features of diabetic kidney disease. ..
  42. Chen J, Long F. mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis. Development. 2014;141:2848-54 pubmed publisher
    ..Disruption of mTORC1 signaling through deletion of either mTOR or the associated protein Raptor greatly diminishes embryonic skeletal growth associated with severe delays in chondrocyte hypertrophy and bone ..
  43. Kaadige M, Yang J, Wilde B, Ayer D. MondoA-Mlx transcriptional activity is limited by mTOR-MondoA interaction. Mol Cell Biol. 2015;35:101-10 pubmed publisher
    ..Collectively, these studies reveal a regulatory relationship between mTOR and the MondoA-TXNIP axis that we propose contributes to glucose homeostasis. ..
  44. Romanino K, Mazelin L, Albert V, Conjard Duplany A, Lin S, Bentzinger C, et al. Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function. Proc Natl Acad Sci U S A. 2011;108:20808-13 pubmed publisher
    ..However, our data also show that the impairment of mitochondria does not lead directly to the lethal myopathy. ..
  45. Sinclair C, Bommakanti G, Gardinassi L, Loebbermann J, Johnson M, Hakimpour P, et al. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation. Science. 2017;357:1014-1021 pubmed publisher
    ..mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. ..
  46. Partovian C, Ju R, Zhuang Z, Martin K, Simons M. Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells. Mol Cell. 2008;32:140-9 pubmed publisher
    ..Thus, S4-dependent targeting of PKCalpha to the plasma membrane is required for recruitment of mTORC2 components to the rafts and Akt activation. ..
  47. Bartolomeo R, Cinque L, De Leonibus C, Forrester A, Salzano A, Monfregola J, et al. mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy. J Clin Invest. 2017;127:3717-3729 pubmed publisher
    ..Taken together, these data unveil a role for mTORC1 and autophagy in the pathogenesis of skeletal disorders and suggest potential therapeutic approaches for the treatment of LSDs. ..
  48. Berezhnoy A, Castro I, Levay A, Malek T, Gilboa E. Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity. J Clin Invest. 2014;124:188-97 pubmed
    ..To specifically target activated cells, we conjugated an siRNA targeting the mTORC1 component raptor to an aptamer that binds 4-1BB, a costimulatory molecule that is expressed on CD8(+) T cells following TCR ..
  49. Frey J, Jacobs B, Goodman C, Hornberger T. A role for Raptor phosphorylation in the mechanical activation of mTOR signaling. Cell Signal. 2014;26:313-22 pubmed publisher
    ..In this study, we set out to determine if changes in the phosphorylation of Raptor contribute to the mechanical activation of mTOR...
  50. Wan M, Leavens K, Saleh D, Easton R, Guertin D, Peterson T, et al. Postprandial hepatic lipid metabolism requires signaling through Akt2 independent of the transcription factors FoxA2, FoxO1, and SREBP1c. Cell Metab. 2011;14:516-27 pubmed publisher
    ..These data show that insulin signaling through Akt2 promotes anabolic lipid metabolism independent of Foxa2 or FoxO1 and through pathways additional to the mTORC1-dependent activation of SREBP1c. ..
  51. Lamming D, Ye L, Katajisto P, Goncalves M, Saitoh M, Stevens D, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638-43 pubmed publisher
    ..Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo. ..
  52. Peng H, Kasada A, Ueno M, Hoshii T, Tadokoro Y, Nomura N, et al. Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self-renewal of hematopoietic stem cells. Biochem Biophys Res Commun. 2018;495:1129-1135 pubmed publisher
    ..In contrast to the severe hematopoietic dysfunction caused by Raptor deletion, which completely inactivates mTORC1, Rheb deficiency in adult mice did not show remarkable hematopoietic ..
  53. Albert V, Cornu M, Hall M. mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior. Biochem Biophys Res Commun. 2015;464:480-6 pubmed publisher
    ..We generated and characterized Agrp neuron-specific raptor knockout (Agrp-raptor KO) mice...
  54. Hoshii T, Kasada A, Hatakeyama T, Ohtani M, Tadokoro Y, Naka K, et al. Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells. Proc Natl Acad Sci U S A. 2014;111:3805-10 pubmed publisher
    ..Deletion of Raptor, an essential component of mTORC1, produced defects in the earliest development of T-cell progenitors in vivo and ..
  55. Kogasaka Y, Hoshino Y, Hiradate Y, Tanemura K, Sato E. Distribution and association of mTOR with its cofactors, raptor and rictor, in cumulus cells and oocytes during meiotic maturation in mice. Mol Reprod Dev. 2013;80:334-48 pubmed publisher
    ..rapamycin (mTOR), a Ser/Thr protein kinase, is the catalytic component of two distinct signaling complexes, mTOR-raptor complex (mTORC1) and mTOR-rictor complex (mTORC2)...
  56. Vijayaraj P, Kröger C, Reuter U, Windoffer R, Leube R, Magin T. Keratins regulate protein biosynthesis through localization of GLUT1 and -3 upstream of AMP kinase and Raptor. J Cell Biol. 2009;187:175-84 pubmed publisher
    ..Analysis of the mammalian target of rapamycin (mTOR) pathway reveals that AMPK induction activates Raptor, repressing protein biosynthesis through mTORC1's downstream targets S6 kinase and 4E-binding protein 1...
  57. Grahammer F, Haenisch N, Steinhardt F, Sandner L, Sander L, Roerden M, et al. mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress. Proc Natl Acad Sci U S A. 2014;111:E2817-26 pubmed publisher
    ..By using constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating ..
  58. Foster K, Acosta Jaquez H, Romeo Y, Ekim B, Soliman G, Carriere A, et al. Regulation of mTOR complex 1 (mTORC1) by raptor Ser863 and multisite phosphorylation. J Biol Chem. 2010;285:80-94 pubmed publisher
    ..To elucidate the poorly defined mechanisms underlying mTORC1 regulation, we have studied the phosphorylation of raptor, an mTOR-interacting partner...
  59. Delgoffe G, Kole T, Cotter R, Powell J. Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation. Mol Immunol. 2009;46:2694-8 pubmed publisher
    ..mTOR signals via two complexes: TORC1, which contains the Regulatory Associated Protein of TOR (raptor), and TORC2, which contains the Rapamycin-insensitive Companion of TOR (rictor)...
  60. Ma L, Tang H, Yin Y, Yu R, Zhao J, Li Y, et al. HDAC5-mTORC1 Interaction in Differential Regulation of Ghrelin and Nucleobindin 2 (NUCB2)/Nesfatin-1. Mol Endocrinol. 2015;29:1571-80 pubmed publisher
    ..HDAC5 coimmunoprecipitated with raptor. Inhibition of HDAC5 by VPA, trichostatin A, or siHDAC5 markedly increased acetylation of raptor Lys840 and ..
  61. Ikenoue T, Inoki K, Yang Q, Zhou X, Guan K. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008;27:1919-31 pubmed publisher
    ..Our study demonstrates that mTORC2 is involved in post-translational processing of PKC by facilitating TM and HM phosphorylation and reveals a novel function of mTORC2 in cellular regulation. ..
  62. Sun C, Southard C, Di Rienzo A. Characterization of a novel splicing variant in the RAPTOR gene. Mutat Res. 2009;662:88-92 pubmed
    ..Raptor, the regulatory associated protein of mTOR, is an important member in this signaling pathway...
  63. Feng D, Youn D, Zhao X, Gao Y, Quinn W, Xiaoli A, et al. mTORC1 Down-Regulates Cyclin-Dependent Kinase 8 (CDK8) and Cyclin C (CycC). PLoS ONE. 2015;10:e0126240 pubmed publisher
    ..Thus, our results suggest that mTORC1 activation in NAFLD and insulin resistance results in down-regulation of the CDK8-CycC complex and elevation of lipogenic protein expression. ..
  64. Hung C, Calejman C, Sanchez Gurmaches J, Li H, Clish C, Hettmer S, et al. Rictor/mTORC2 loss in the Myf5 lineage reprograms brown fat metabolism and protects mice against obesity and metabolic disease. Cell Rep. 2014;8:256-71 pubmed publisher
    ..Our findings provide insights into the signaling circuitry that regulates brown adipocytes and could have important implications for developing therapies aimed at increasing energy expenditure as a means to combat human obesity. ..
  65. Lee P, Sykes D, Ameri S, Kalaitzidis D, Charles J, Nelson Maney N, et al. The metabolic regulator mTORC1 controls terminal myeloid differentiation. Sci Immunol. 2017;2: pubmed publisher
    ..Confirmatory studies using mice with inducible deletion of the mTORC1 component Raptor demonstrated absence of mature circulating monocytes, as well as disruption in neutrophil and dendritic cell ..
  66. Wolff N, Vega Rubin de Celis S, Xie X, Castrillon D, Kabbani W, Brugarolas J. Cell-type-dependent regulation of mTORC1 by REDD1 and the tumor suppressors TSC1/TSC2 and LKB1 in response to hypoxia. Mol Cell Biol. 2011;31:1870-84 pubmed publisher
    ..Hypoxia signaling in hepatocytes involves Lkb1, AMP-activated protein kinase (AMPK), and raptor. Differences in signal relay extend beyond hypoxia and involve AMPK signaling...
  67. Gorre N, Adhikari D, Lindkvist R, Brännström M, Liu K, Shen Y. mTORC1 Signaling in oocytes is dispensable for the survival of primordial follicles and for female fertility. PLoS ONE. 2014;9:e110491 pubmed publisher
    ..development and fertility in female mice, we conditionally deleted the specific and essential mTORC1 component Rptor (regulatory-associated protein of mTORC1) from the oocytes of primordial follicles by using transgenic mice ..
  68. Wang S, Amato K, Song W, Youngblood V, Lee K, Boothby M, et al. Regulation of endothelial cell proliferation and vascular assembly through distinct mTORC2 signaling pathways. Mol Cell Biol. 2015;35:1299-313 pubmed publisher
    ..and mTORC2, whose activities and substrate specificities are regulated by complex specific cofactors, including Raptor and Rictor, respectively...
  69. Inoki K, Mori H, Wang J, Suzuki T, Hong S, Yoshida S, et al. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice. J Clin Invest. 2011;121:2181-96 pubmed publisher
    ..These results indicate that mTORC1 activation in podocytes is a critical event in inducing DN and suggest that reduction of podocyte mTORC1 activity is a potential therapeutic strategy to prevent DN. ..
  70. Aladegbami B, Barron L, Bao J, Colasanti J, Erwin C, Warner B, et al. Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine. Sci Rep. 2017;7:5580 pubmed publisher
    ..When Raptor, a critical scaffold protein for mammalian target of rapamycin complex 1 (mTORC1), was acutely deleted in ..
  71. Dennis M, Kimball S, Jefferson L. Mechanistic target of rapamycin complex 1 (mTORC1)-mediated phosphorylation is governed by competition between substrates for interaction with raptor. J Biol Chem. 2013;288:10-9 pubmed publisher
    ..of mTORC1 suggested that elevated phosphorylation was the result of enhanced interaction of p70S6K1 with raptor. These findings were extended to a cell culture system wherein loss of 4E-BP1 and 4E-BP2 resulted in elevated ..
  72. Figlia G, Norrmen C, Pereira J, Gerber D, Suter U. Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system. elife. 2017;6: pubmed publisher
    ..An ensuing decline in mTORC1 activity is crucial to allow myelination to start, while remaining mTORC1 activity drives myelin growth. ..
  73. Yang K, Shrestha S, Zeng H, Karmaus P, Neale G, Vogel P, et al. T cell exit from quiescence and differentiation into Th2 cells depend on Raptor-mTORC1-mediated metabolic reprogramming. Immunity. 2013;39:1043-56 pubmed publisher
    ..Here we describe that Raptor-mTORC1-dependent metabolic reprogramming is a central determinant of this transitional process...
  74. Wieman H, Wofford J, Rathmell J. Cytokine stimulation promotes glucose uptake via phosphatidylinositol-3 kinase/Akt regulation of Glut1 activity and trafficking. Mol Biol Cell. 2007;18:1437-46 pubmed
    ..may regulate Glut1, we analyzed the role of Akt activation of mammalian target of rapamycin (mTOR)/regulatory associated protein of mTOR (RAPTOR) and inhibition of glycogen synthase kinase (GSK)3...
  75. Bercury K, Dai J, Sachs H, Ahrendsen J, Wood T, Macklin W. Conditional ablation of raptor or rictor has differential impact on oligodendrocyte differentiation and CNS myelination. J Neurosci. 2014;34:4466-80 pubmed publisher
    ..mTOR functions through two distinct complexes, mTOR complex 1 (mTORC1) and mTORC2, by binding to either Raptor or Rictor, respectively...
  76. Venkatesh A, Ma S, Le Y, Hall M, Rüegg M, Punzo C. Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice. J Clin Invest. 2015;125:1446-58 pubmed publisher
    ..Together, the results of this study address a longstanding question in the field and suggest that activating mTORC1 in cones has therapeutic potential to prolong vision in RP. ..
  77. Yang M, Chen S, Du J, He J, Wang Y, Li Z, et al. NK cell development requires Tsc1-dependent negative regulation of IL-15-triggered mTORC1 activation. Nat Commun. 2016;7:12730 pubmed publisher
    ..Deletion of Raptor, a component of mTORC1, largely reverses these defects...
  78. Limon J, So L, Jellbauer S, Chiu H, Corado J, Sykes S, et al. mTOR kinase inhibitors promote antibody class switching via mTORC2 inhibition. Proc Natl Acad Sci U S A. 2014;111:E5076-85 pubmed publisher
    ..These observations emphasize the distinct actions of TOR-KIs compared with rapamycin and suggest that TOR-KIs might be useful to enhance production of class-switched antibodies following vaccination. ..
  79. Tzatsos A. Raptor binds the SAIN (Shc and IRS-1 NPXY binding) domain of insulin receptor substrate-1 (IRS-1) and regulates the phosphorylation of IRS-1 at Ser-636/639 by mTOR. J Biol Chem. 2009;284:22525-34 pubmed publisher
    ..Here, it has been shown that knockdown of mTOR, Raptor, and mLST8, but not Rictor and mSin1, suppresses insulin-stimulated phosphorylation of IRS-1 at Ser-636/639 and ..
  80. Guridi M, Tintignac L, Lin S, Kupr B, Castets P, Rüegg M. Activation of mTORC1 in skeletal muscle regulates whole-body metabolism through FGF21. Sci Signal. 2015;8:ra113 pubmed publisher
    ..Thus, sustained activation of mTORC1 signaling in skeletal muscle regulated whole-body metabolism through the induction of FGF21, which, over the long term, caused severe lipodystrophy. ..
  81. Mounier R, Lantier L, Leclerc J, Sotiropoulos A, Foretz M, Viollet B. Antagonistic control of muscle cell size by AMPK and mTORC1. Cell Cycle. 2011;10:2640-6 pubmed
    ..Thus, the crosstalk between AMPK and mTORC1 signaling is a highly regulated way to control changes in muscle growth and metabolic rate imposed by external cues. ..
  82. Su K, Cao J, Tang Z, Dai S, He Y, Sampson S, et al. HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth. Nat Cell Biol. 2016;18:527-39 pubmed publisher
    ..On activation by proteotoxic stress, JNK phosphorylates both RAPTOR at S863 and mTOR at S567, causing partial disintegration of mTORC1 and subsequent translation inhibition...
  83. Ma S, Venkatesh A, Langellotto F, Le Y, Hall M, Rüegg M, et al. Loss of mTOR signaling affects cone function, cone structure and expression of cone specific proteins without affecting cone survival. Exp Eye Res. 2015;135:1-13 pubmed publisher
    ..is found in two distinct complexes (mTORC1 & mTORC2) that are characterized by their unique accessory proteins RAPTOR and RICTOR respectively...
  84. Ghosh P, Wu M, Zhang H, Sun H. mTORC1 signaling requires proteasomal function and the involvement of CUL4-DDB1 ubiquitin E3 ligase. Cell Cycle. 2008;7:373-81 pubmed
    ..both of which contain the catalytic subunit mTOR, the invariable subunit mLST8, and a complex specific subunit Raptor or Rictor, forming either the rapamycin-sensitive mTORC1 or rapamycin-insensitive mTORC2, respectively...