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Gene Review

RPTOR  -  regulatory associated protein of MTOR,...

Homo sapiens

Synonyms: KIAA1303, KOG1, Mip1, RAPTOR, Raptor, ...
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Disease relevance of KIAA1303

  • Signaling mediated by the mammalian target of rapamycin kinase (mTOR) is activated during human cytomegalovirus (HCMV) infection. mTOR is found in two complexes differing by the binding partner, rictor or raptor [1].
  • However, the efficacy of mTOR inhibitors alone in the treatment of patients with malignant gliomas is only modest, potentially because these agents rather than acting as mTOR kinase inhibitors instead interfere with the function of only mTOR/raptor (regulatory-associated protein of mTOR) complex and thus do not perturb all mTOR functions [2].
  • Hypersensitivity pneumonitis in a raptor handler and a wild bird fancier [3].
  • Raptor species at risk from lead poisoning, including some of high conservation value, are described, and future priorities for lead poisoning research and policy are suggested [4].
  • The aim of this epidemiological study was to investigate the seroprevalence of FHV-1 and owl herpesvirus (Strigid herpesvirus-1; StHV-1) infection in the UK, using virus neutralization tests, and to evaluate the prevalence of herpesvirus infection in captive and wild raptor populations [5].

High impact information on KIAA1303

  • Cell stimulation promotes mTOR/raptor binding to the eIF3 complex and phosphorylation of S6K1 at its hydrophobic motif [6].
  • mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery [7].
  • We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels [7].
  • We identify PRAS40 as a raptor-interacting protein that binds to mTORC1 in insulin-deprived cells and whose in vitro interaction with mTORC1 is disrupted by high salt concentrations [8].
  • When bound to FKBP12, rapamycin interacts with and inhibits the kinase activity of a multiprotein complex composed of mTOR, mLST8, and raptor (mTORC1) [9].

Biological context of KIAA1303


Anatomical context of KIAA1303


Associations of KIAA1303 with chemical compounds

  • Caffeine, wortmannin, LY294002, and rapamycin-FKBP12 also markedly inhibited mTOR activity in vitro, but unlike FTS, none of the other mTOR inhibitors appreciably changed the amount of raptor associated with mTOR [18].
  • Our results demonstrate the importance of localized PA generation for the mitogen-induced activation of mTOR, which is achieved by a specific interaction between PLD2 and mTOR/raptor [19].
  • 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 [20].
  • Raptor species in the Americas are recovering since restrictions on the use of dichlorodiphenyltrichloroethane (DDT) and the implementation of conservation measures, in effect constituting a hemisphere-wide predator-reintroduction experiment, and profound effects on populations of their prey are to be expected [21].
  • The underlying technology (software Quasar and Raptor, respectively) specifically allows for induced fit, solvation phenomena and entropic effects [22].

Physical interactions of KIAA1303


Regulatory relationships of KIAA1303

  • Raptor has a positive role in nutrient-stimulated signaling to the downstream effector S6K1, maintenance of cell size, and mTOR protein expression [7].

Other interactions of KIAA1303


Analytical, diagnostic and therapeutic context of KIAA1303


  1. Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes. Kudchodkar, S.B., Yu, Y., Maguire, T.G., Alwine, J.C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Silencing mammalian target of rapamycin signaling by small interfering RNA enhances rapamycin-induced autophagy in malignant glioma cells. Iwamaru, A., Kondo, Y., Iwado, E., Aoki, H., Fujiwara, K., Yokoyama, T., Mills, G.B., Kondo, S. Oncogene (2007) [Pubmed]
  3. Hypersensitivity pneumonitis in a raptor handler and a wild bird fancier. Choy, A.C., Patterson, R., Ray, A.H., Roberts, M. Ann. Allergy Asthma Immunol. (1995) [Pubmed]
  4. Lead poisoning of raptors in France and elsewhere. Pain, D.J., Amiard-Triquet, C. Ecotoxicol. Environ. Saf. (1993) [Pubmed]
  5. Investigation into the seroprevalence of falcon herpesvirus antibodies in raptors in the UK using virus neutralization tests and different herpesvirus isolates. Zsivanovits, P., Forbes, N.A., Zvonar, L.T., Williams, M.R., Lierz, M., Prusas, C., Hafez, M.M. Avian Pathol. (2004) [Pubmed]
  6. mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Holz, M.K., Ballif, B.A., Gygi, S.P., Blenis, J. Cell (2005) [Pubmed]
  7. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Kim, D.H., Sarbassov, D.D., Ali, S.M., King, J.E., Latek, R.R., Erdjument-Bromage, H., Tempst, P., Sabatini, D.M. Cell (2002) [Pubmed]
  8. PRAS40 Is an Insulin-Regulated Inhibitor of the mTORC1 Protein Kinase. Sancak, Y., Thoreen, C.C., Peterson, T.R., Lindquist, R.A., Kang, S.A., Spooner, E., Carr, S.A., Sabatini, D.M. Mol. Cell (2007) [Pubmed]
  9. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Sarbassov, d.o.s. .D., Ali, S.M., Sengupta, S., Sheen, J.H., Hsu, P.P., Bagley, A.F., Markhard, A.L., Sabatini, D.M. Mol. Cell (2006) [Pubmed]
  10. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Tzatsos, A., Kandror, K.V. Mol. Cell. Biol. (2006) [Pubmed]
  11. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. Nojima, H., Tokunaga, C., Eguchi, S., Oshiro, N., Hidayat, S., Yoshino, K., Hara, K., Tanaka, N., Avruch, J., Yonezawa, K. J. Biol. Chem. (2003) [Pubmed]
  12. Rheb binds and regulates the mTOR kinase. Long, X., Lin, Y., Ortiz-Vega, S., Yonezawa, K., Avruch, J. Curr. Biol. (2005) [Pubmed]
  13. Rapamycin inhibits cell motility by suppression of mTOR-mediated S6K1 and 4E-BP1 pathways. Liu, L., Li, F., Cardelli, J.A., Martin, K.A., Blenis, J., Huang, S. Oncogene (2006) [Pubmed]
  14. Different roles for the TOS and RAIP motifs of the translational regulator protein 4E-BP1 in the association with raptor and phosphorylation by mTOR in the regulation of cell size. Eguchi, S., Tokunaga, C., Hidayat, S., Oshiro, N., Yoshino, K., Kikkawa, U., Yonezawa, K. Genes Cells (2006) [Pubmed]
  15. Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation. Vos, J.G., Dybing, E., Greim, H.A., Ladefoged, O., Lambré, C., Tarazona, J.V., Brandt, I., Vethaak, A.D. Crit. Rev. Toxicol. (2000) [Pubmed]
  16. Species variation in osmotic, cryoprotectant, and cooling rate tolerance in poultry, eagle, and peregrine falcon spermatozoa. Blanco, J.M., Gee, G., Wildt, D.E., Donoghue, A.M. Biol. Reprod. (2000) [Pubmed]
  17. Improved fluoroimmunoassays using the dye Alexa Fluor 647 with the RAPTOR, a fiber optic biosensor. Anderson, G.P., Nerurkar, N.L. J. Immunol. Methods (2002) [Pubmed]
  18. Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity both in cells and in vitro by promoting dissociation of the mTOR-raptor complex. McMahon, L.P., Yue, W., Santen, R.J., Lawrence, J.C. Mol. Endocrinol. (2005) [Pubmed]
  19. PLD2 forms a functional complex with mTOR/raptor to transduce mitogenic signals. Ha, S.H., Kim, D.H., Kim, I.S., Kim, J.H., Lee, M.N., Lee, H.J., Kim, J.H., Jang, S.K., Suh, P.G., Ryu, S.H. Cell. Signal. (2006) [Pubmed]
  20. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. Long, X., Ortiz-Vega, S., Lin, Y., Avruch, J. J. Biol. Chem. (2005) [Pubmed]
  21. Western sandpipers have altered migration tactics as peregrine falcon populations have recovered. Ydenberg, R.C., Butler, R.W., Lank, D.B., Smith, B.D., Ireland, J. Proc. Biol. Sci. (2004) [Pubmed]
  22. In silico prediction of harmful effects triggered by drugs and chemicals. Vedani, A., Dobler, M., Lill, M.A. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
  23. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Schalm, S.S., Fingar, D.C., Sabatini, D.M., Blenis, J. Curr. Biol. (2003) [Pubmed]
  24. Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence for association despite adequate power and evidence for linkage. Stuart, P., Nair, R.P., Abecasis, G.R., Nistor, I., Hiremagalore, R., Chia, N.V., Qin, Z.S., Thompson, R.A., Jenisch, S., Weichenthal, M., Janiga, J., Lim, H.W., Christophers, E., Voorhees, J.J., Elder, J.T. J. Med. Genet. (2006) [Pubmed]
  25. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Oshiro, N., Yoshino, K., Hidayat, S., Tokunaga, C., Hara, K., Eguchi, S., Avruch, J., Yonezawa, K. Genes Cells (2004) [Pubmed]
  26. Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. Kimball, S.R., Jefferson, L.S. J. Nutr. (2006) [Pubmed]
  27. Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis. Capon, F., Helms, C., Veal, C.D., Tillman, D., Burden, A.D., Barker, J.N., Bowcock, A.M., Trembath, R.C. J. Med. Genet. (2004) [Pubmed]
  28. Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1. Wang, L., Rhodes, C.J., Lawrence, J.C. J. Biol. Chem. (2006) [Pubmed]
  29. Raptor protein contains a caspase-like domain. Ginalski, K., Zhang, H., Grishin, N.V. Trends Biochem. Sci. (2004) [Pubmed]
  30. Epornitic of avian pox in a raptor rehabilitation center. Wheeldon, E.B., Sedgwick, C.J., Schulz, T.A. J. Am. Vet. Med. Assoc. (1985) [Pubmed]
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