Beyond control of protein translation: What we have learned about the non-canonical regulation and function of mammalian target of rapamycin (mTOR)

Biochimica et Biophysica Acta - Proteins and Proteomics

Volumn 1834, Issue 7, 2013, Pages 1434-1448

  Malik, Anna R ^a   Urbanska, Malgorzata ^a   MacIas, Matylda ^a   Skalecka, Agnieszka ^a   Jaworski, Jacek ^a  

^a INTERNATIONAL INSTITUTE OF MOLECULAR AND CELL BIOLOGY   (Poland)

Author keywords

Cytoskeleton dynamics; Membrane trafficking; mTOR; Rapamycin; Transcription; Translation

Indexed keywords

AMINO ACID; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN 14 3 3;

CELLULAR DISTRIBUTION; CYTOSKELETON; FEEDBACK SYSTEM; GENETIC TRANSCRIPTION; HUMAN; LYSOSOME; MEMBRANE BIOLOGY; MEMBRANE TRAFFICKING; NONHUMAN; POSTTRANSCRIPTIONAL GENE SILENCING; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; REVIEW; RNA TRANSLATION; TRANSCRIPTION REGULATION;

ANIMALS; CELL NUCLEUS; CELL PHYSIOLOGICAL PROCESSES; CELLULAR MICROENVIRONMENT; HUMANS; LYSOSOMES; MODELS, BIOLOGICAL; PROTEIN BIOSYNTHESIS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES;

MAMMALIA;

EID: 84878880159     PISSN: 15709639     EISSN: 18781454     Source Type: Journal    
DOI: 10.1016/j.bbapap.2012.12.010     Document Type: Review

References (195)

1. E.A. Dunlop, and A.R. Tee Mammalian target of rapamycin complex 1: signalling inputs, substrates and feedback mechanisms Cell. Signal. 21 2009 827 835
2. N. Hay, and N. Sonenberg Upstream and downstream of mTOR Genes Dev. 18 2004 1926 1945 (Pubitemid 39071573)
3. L. Swiech, M. Perycz, A. Malik, and J. Jaworski Role of mTOR in physiology and pathology of the nervous system Biochim. Biophys. Acta 1784 2008 116 132
4. T. Weichhart Mammalian target of rapamycin: a signaling kinase for every aspect of cellular life Methods Mol. Biol. 821 2012 1 14
5. R. Zoncu, A. Efeyan, and D.M. Sabatini mTOR: from growth signal integration to cancer, diabetes and ageing Nat. Rev. Mol. Cell Biol. 12 2011 21 35
6. K.G. Foster, and D.C. Fingar Mammalian target of rapamycin (mTOR): conducting the cellular signaling symphony J. Biol. Chem. 285 2010 14071 14077
7. S. Sengupta, T.R. Peterson, and D.M. Sabatini Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress Mol. Cell 40 2010 310 322
8. M. Laplante, and D.M. Sabatini mTOR signaling in growth control and disease Cell 149 2012 274 293
9. H.B. Jefferies, S. Fumagalli, P.B. Dennis, C. Reinhard, R.B. Pearson, and G. Thomas Rapamycin suppresses 5′TOP mRNA translation through inhibition of p70s6k EMBO J. 16 1997 3693 3704 (Pubitemid 27250062)
10. D.H. Kim, D.D. Sarbassov, S.M. Ali, J.E. King, R.R. Latek, H. Erdjument-Bromage, P. Tempst, and D.M. Sabatini mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery Cell 110 2002 163 175 (Pubitemid 34876545)
11. K. Hara, Y. Maruki, X. Long, K. Yoshino, N. Oshiro, S. Hidayat, C. Tokunaga, J. Avruch, and K. Yonezawa Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action Cell 110 2002 177 189 (Pubitemid 34876546)
12. E. Jacinto, R. Loewith, A. Schmidt, S. Lin, M.A. Rüegg, A. Hall, and M.N. Hall Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive Nat. Cell Biol. 6 2004 1122 1128 (Pubitemid 39468014)
13. D.D. Sarbassov, S.M. Ali, D.-H. Kim, D.A. Guertin, R.R. Latek, H. Erdjument-Bromage, P. Tempst, and D.M. Sabatini Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton Curr. Biol. 14 2004 1296 1302 (Pubitemid 38991819)
14. T. Kaizuka, T. Hara, N. Oshiro, U. Kikkawa, K. Yonezawa, K. Takehana, S. Iemura, T. Natsume, and N. Mizushima Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly J. Biol. Chem. 285 2010 20109 20116
15. T.R. Peterson, M. Laplante, C.C. Thoreen, Y. Sancak, S.A. Kang, W.M. Kuehl, N.S. Gray, and D.M. Sabatini DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival Cell 137 2009 873 886
16. D.H. Kim, D.D. Sarbassov, S.M. Ali, R.R. Latek, K.V. Guntur, H. Erdjument-Bromage, P. Tempst, and D.M. Sabatini GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR Mol. Cell 11 2003 895 904 (Pubitemid 36566312)
17. E. Vander Haar, S.I. Lee, S. Bandhakavi, T.J. Griffin, and D.H. Kim Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40 Nat. Cell Biol. 9 2007 316 323 (Pubitemid 46344611)
18. L. Wang, T.E. Harris, R.A. Roth, and J.C. Lawrence Jr. PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding J. Biol. Chem. 282 2007 20036 20044 (Pubitemid 47100127)
19. M.A. Frias, C.C. Thoreen, J.D. Jaffe, W. Schroder, T. Sculley, S.A. Carr, and D.M. Sabatini mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s Curr. Biol. 16 2006 1865 1870 (Pubitemid 44354144)
20. L.R. Pearce, X. Huang, J. Boudeau, R. Pawlowski, S. Wullschleger, M. Deak, A. Ibrahim, R. Gourlay, M.A. Magnuson, and D.R. Alessi Identification of Protor as a novel Rictor-binding component of mTOR-complex-2 Biochem. J. 405 2007 513 522 (Pubitemid 47172049)
21. K. Thedieck, P. Polak, M.L. Kim, K.D. Molle, A. Cohen, P. Jenö, C. Arrieumerlou, and M.N. Hall PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis PLoS One 2 2007
22. X. Gan, J. Wang, C. Wang, E. Sommer, T. Kozasa, S. Srinivasula, D. Alessi, S. Offermanns, M.I. Simon, and D. Wu PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12 Nat. Cell Biol. 14 2012 686 696
23. D.D. Sarbassov, S.M. Ali, S. Sengupta, J.H. Sheen, P.P. Hsu, A.F. Bagley, A.L. Markhard, and D.M. Sabatini Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB Mol. Cell 22 2006 159 168
24. M. Urbanska, A. Gozdz, L.J. Swiech, and J. Jaworski Mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) control the dendritic arbor morphology of hippocampal neurons J. Biol. Chem. 287 2012 30240 30256
25. R.J. Dowling, I. Topisirovic, B.D. Fonseca, and N. Sonenberg Dissecting the role of mTOR: lessons from mTOR inhibitors Biochim. Biophys. Acta 1804 2010 433 439
26. C.C. Thoreen, and D.M. Sabatini Rapamycin inhibits mTORC1, but not completely Autophagy 5 2009 725 726
27. C.C. Thoreen, S.A. Kang, J.W. Chang, Q. Liu, J. Zhang, Y. Gao, L.J. Reichling, T. Sim, D.M. Sabatini, and N.S. Gray An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1 J. Biol. Chem. 284 2009 8023 8032
28. M.E. Feldman, B. Apsel, A. Uotila, R. Loewith, Z.A. Knight, D. Ruggero, and K.M. Shokat Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2 PLoS Biol. 7 2009 e38
29. W.J. Oh, and E. Jacinto mTOR complex 2 signaling and functions Cell Cycle (Georgetown, Tex.) 10 2011 2305 2316
30. C. De Virgilio, and R. Loewith The TOR signalling network from yeast to man Int. J. Biochem. Cell Biol. 38 2006 1476 1481 (Pubitemid 43729300)
31. R. Loewith, and M.N. Hall Target of rapamycin (TOR) in nutrient signaling and growth control Genetics 189 2011 1177 1201
32. S. Wullschleger, R. Loewith, and M.N. Hall TOR signaling in growth and metabolism Cell 124 2006 471 484 (Pubitemid 43199434)
33. M.N. Corradetti, and K.L. Guan Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 25 2006 6347 6360 (Pubitemid 44582281)
34. P.T. Bhaskar, and N. Hay The two TORCs and Akt Dev. Cell 12 2007 487 502 (Pubitemid 46523652)
35. L. Swiech, M. Urbanska, M. Macias, A. Skalecka, and J. Jaworski Mammalian Target of Rapamycin H. Mukai, Protein Kinase Technologies, Neuromethods 68 2012 291 318
36. M.G. Garelick, and B.K. Kennedy TOR on the brain. Exp. Gerontol. 46 2011 155 163
37. M. Kleijn, M.M. Korthout, H.O. Voorma, and A.A. Thomas Phosphorylation of the eIF4E-binding protein PHAS-I after exposure of PC12 cells to EGF and NGF FEBS Lett. 396 1996 165 171 (Pubitemid 26377818)
38. G.J. Brunn, C.C. Hudson, A. Sekulic, J.M. Williams, H. Hosoi, P.J. Houghton, J.C. Lawrence Jr., and R.T. Abraham Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin Science 277 1997 99 101 (Pubitemid 27450655)
39. S. Lamouille, E. Connolly, J.W. Smyth, R.J. Akhurst, and R. Derynck TGF-β-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion J. Cell Sci. 125 2012 1259 1273
40. C.M. Dunaway, Y. Hwang, C.W. Lindsley, R.S. Cook, J.Y. Wu, M. Boothby, J. Chen, and D.M. Brantley-Sieders Cooperative signaling between Slit2 and Ephrin-A1 regulates a balance between angiogenesis and angiostasis Mol. Cell. Biol. 31 2011 404 416
41. H.S. Kuehn, M.-Y. Jung, M.A. Beaven, D.D. Metcalfe, and A.M. Gilfillan Prostaglandin E2 activates and utilizes mTORC2 as a central signaling locus for the regulation of mast cell chemotaxis and mediator release J. Biol. Chem. 286 2011 391 402
42. C. Partovian, R. Ju, Z.W. Zhuang, K.A. Martin, and M. Simons Syndecan-4 regulates subcellular localization of mTOR Complex2 and Akt activation in a PKCalpha-dependent manner in endothelial cells Mol. Cell 32 2008 140 149
43. Z. Fang, T. Zhang, N. Dizeyi, S. Chen, H. Wang, K.D. Swanson, C. Cai, S.P. Balk, and X. Yuan Androgen receptor enhances p27 degradation in prostate cancer cells through rapid and selective TORC2 activation J. Biol. Chem. 287 2012 2090 2098
44. E.M. Smith, S.G. Finn, A.R. Tee, G.J. Browne, and C.G. Proud 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. 280 2005 18717 18727 (Pubitemid 41379573)
45. K. Inoki, Y. Li, T. Xu, and K.L. Guan Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling Genes Dev. 17 2003 1829 1834 (Pubitemid 36944560)
46. Q. Yang, K. Inoki, E. Kim, and K.L. Guan TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity Proc. Natl. Acad. Sci. U.S.A. 103 2006 6811 6816
47. J. Huang, C.C. Dibble, M. Matsuzaki, and B.D. Manning The TSC1-TSC2 complex is required for proper activation of mTOR complex 2 Mol. Cell. Biol. 28 2008 4104 4115 (Pubitemid 351812994)
48. R.P. Carson, D.L. Van Nielen, P.A. Winzenburger, and K.C. Ess Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin Neurobiol. Dis. 45 2012 369 380
49. B.D. Manning Comment on "A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation": building a model of the mTOR signaling network with a potentially faulty tool Sci. Signal. 5 2012 (lc3; author reply lc4)
50. P. Dalle Pezze, A.G. Sonntag, A. Thien, M.T. Prentzell, M. Godel, S. Fischer, E. Neumann-Haefelin, T.B. Huber, R. Baumeister, D.P. Shanley, and K. Thedieck A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation Sci. Signal. 5 2012 ra25
51. K. Hara, K. Yonezawa, Q.P. Weng, M.T. Kozlowski, C. Belham, and J. Avruch Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism J. Biol. Chem. 273 1998 14484 14494 (Pubitemid 28319170)
52. Y. Sancak, T.R. Peterson, Y.D. Shaul, R.A. Lindquist, C.C. Thoreen, L. Bar-Peled, and D.M. Sabatini The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 Science 320 2008 1496 1501 (Pubitemid 351929429)
53. Y. Sancak, L. Bar-Peled, R. Zoncu, A.L. Markhard, S. Nada, and D.M. Sabatini Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids Cell 141 2010 290 303
54. L. Bar-Peled, L.D. Schweitzer, R. Zoncu, and D.M. Sabatini Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1 Cell 150 2012 1196 1208
55. R. Zoncu, L. Bar-Peled, A. Efeyan, S. Wang, Y. Sancak, and D.M. Sabatini mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase Science 334 2011 678 683
56. M.H. Ögmundsdóttir, S. Heublein, S. Kazi, B. Reynolds, S.M. Visvalingam, M.K. Shaw, and D.C.I. Goberdhan Proton-assisted amino acid transporter PAT1 complexes with Rag GTPases and activates TORC1 on late endosomal and lysosomal membranes PLoS One 7 2012
57. A. Duran, R. Amanchy, J.F. Linares, J. Joshi, S. Abu-Baker, A. Porollo, M. Hansen, J. Moscat, and M.T. Diaz-Meco p62 is a key regulator of nutrient sensing in the mTORC1 pathway Mol. Cell 44 2011 134 146
58. J.M. Han, S.J. Jeong, M.C. Park, G. Kim, N.H. Kwon, H.K. Kim, S.H. Ha, S.H. Ryu, and S. Kim Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway Cell 149 2012 410 424
59. V.I. Korolchuk, S. Saiki, M. Lichtenberg, F.H. Siddiqi, E.A. Roberts, S. Imarisio, L. Jahreiss, S. Sarkar, M. Futter, F.M. Menzies, C.J. O'Kane, V. Deretic, and D.C. Rubinsztein Lysosomal positioning coordinates cellular nutrient responses Nat. Cell Biol. 13 2011 453 460
60. R.J. Flinn, Y. Yan, S. Goswami, P.J. Parker, and J.M. Backer The late endosome is essential for mTORC1 signaling Mol. Biol. Cell 21 2010 833 841
61. 2 +/CaM signaling to hVps34 Cell Metab. 7 2008 456 465 (Pubitemid 351598024)
62. T. Nobukuni, M. Joaquin, M. Roccio, S.G. Dann, S.Y. Kim, P. Gulati, M.P. Byfield, J.M. Backer, F. Natt, J.L. Bos, F.J. Zwartkruis, and G. Thomas Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase Proc. Natl. Acad. Sci. U.S.A. 102 2005 14238 14243 (Pubitemid 41429682)
63. I. Tato, R. Bartrons, F. Ventura, and J.L. Rosa Amino acids activate mammalian target of rapamycin complex 2 (mTORC2) via PI3K/Akt signaling J. Biol. Chem. 286 2011 6128 6142
64. C.-Y. Wang, H.-H. Kim, Y. Hiroi, N. Sawada, S. Salomone, L.E. Benjamin, K. Walsh, M.A. Moskowitz, and J.K. Liao Obesity increases vascular senescence and susceptibility to ischemic injury through chronic activation of Akt and mTOR Sci. Signal. 2 2009
65. S. Aronova, K. Wedaman, S. Anderson, J. Yates 3rd, and T. Powers Probing the membrane environment of the TOR kinases reveals functional interactions between TORC1, actin, and membrane trafficking in Saccharomyces cerevisiae Mol. Biol. Cell 18 2007 2779 2794 (Pubitemid 47235287)
66. T.W. Sturgill, A. Cohen, M. Diefenbacher, M. Trautwein, D.E. Martin, and M.N. Hall TOR1 and TOR2 have distinct locations in live cells Eukaryot. Cell 7 2008 1819 1830
67. D. Berchtold, and T.C. Walther TORC2 plasma membrane localization is essential for cell viability and restricted to a distinct domain Mol. Biol. Cell 20 2009 1565 1575
68. L. Li, E. Kim, H. Yuan, K. Inoki, P. Goraksha-Hicks, R.L. Schiesher, T.P. Neufeld, and K.L. Guan Regulation of mTORC1 by the Rab and Arf GTPases J. Biol. Chem. 285 2010 19705 19709
69. A. Saci, L.C. Cantley, and C.L. Carpenter Rac1 regulates the activity of mTORC1 and mTORC2 and controls cellular size Mol. Cell 42 2011 50 61
70. X. Liu, and X.F.S. Zheng Endoplasmic reticulum and Golgi localization sequences for mammalian target of rapamycin Mol. Biol. Cell 18 2007 1073 1082 (Pubitemid 46399510)
71. R.M. Drenan, X. Liu, P.G. Bertram, and X.F. Zheng FKBP12-rapamycin- associated protein or mammalian target of rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi apparatus J. Biol. Chem. 279 2004 772 778 (Pubitemid 38044883)
72. D.R. Boulbés, T. Shaiken, and D.D. Sarbassov Endoplasmic reticulum is a main localization site of mTORC2 Biochem. Biophys. Res. Commun. 413 2011 46 52
73. V. Zinzalla, D. Stracka, W. Oppliger, and M.N. Hall Activation of mTORC2 by association with the ribosome Cell 144 2011 757 768
74. W.J. Oh, C.C. Wu, S.J. Kim, V. Facchinetti, L.A. Julien, M. Finlan, P.P. Roux, B. Su, and E. Jacinto mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide EMBO J. 29 2010 3939 3951
75. H. Li, C.K. Tsang, M. Watkins, P.G. Bertram, and X.F. Zheng Nutrient regulates Tor1 nuclear localization and association with rDNA promoter Nature 442 2006 1058 1061 (Pubitemid 44330265)
76. J.E. Kim, and J. Chen Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation Proc. Natl. Acad. Sci. U.S.A. 97 2000 14340 14345 (Pubitemid 32016577)
77. X. Zhang, L. Shu, H. Hosoi, K.G. Murti, and P.J. Houghton Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture J. Biol. Chem. 277 2002 28127 28134 (Pubitemid 34966765)
78. M. Rosner, and M. Hengstschlager 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. 17 2008 2934 2948
79. R.A. Bachmann, J.H. Kim, A.L. Wu, I.H. Park, and J. Chen A nuclear transport signal in mammalian target of rapamycin is critical for its cytoplasmic signaling to S6 kinase 1 J. Biol. Chem. 281 2006 7357 7363 (Pubitemid 43847505)
80. R. Bernardi, I. Guernah, D. Jin, S. Grisendi, A. Alimonti, J. Teruya-Feldstein, C. Cordon-Cardo, M.C. Simon, S. Rafii, and P.P. Pandolfi PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR Nature 442 2006 779 785 (Pubitemid 44258904)
81. Y. Li, K. Inoki, R. Yeung, and K.L. Guan Regulation of TSC2 by 14-3-3 binding J. Biol. Chem. 277 2002 44593 44596 (Pubitemid 36159047)
82. D.M. Gwinn, D.B. Shackelford, D.F. Egan, M.M. Mihaylova, A. Mery, D.S. Vasquez, B.E. Turk, and R.J. Shaw AMPK phosphorylation of raptor mediates a metabolic checkpoint Mol. Cell 30 2008 214 226 (Pubitemid 351626684)
83. M.P. DeYoung, P. Horak, A. Sofer, D. Sgroi, and L.W. Ellisen Hypoxia regulates TSC1/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling Genes Dev. 22 2008 239 251
84. C.C. Dibble, J.M. Asara, and B.D. Manning Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1 Mol. Cell. Biol. 29 2009 5657 5670
85. C. Treins, P.H. Warne, M.A. Magnuson, M. Pende, and J. Downward Rictor is a novel target of p70 S6 kinase-1 Oncogene 29 2010 1003 1016
86. S. Yoshida, S. Hong, T. Suzuki, S. Nada, A.M. Mannan, J. Wang, M. Okada, K.-L. Guan, and K. Inoki Redox regulates mammalian target of rapamycin complex 1 (mTORC1) activity by modulating the TSC1/TSC2-Rheb GTPase pathway J. Biol. Chem. 286 2011 32651 32660
87. B.K. Nayak, D. Feliers, S. Sudarshan, W.E. Friedrichs, R.T. Day, D.D. New, J.P. Fitzgerald, A. Eid, T. Denapoli, D.J. Parekh, Y. Gorin, K. Block, Stabilization of HIF-2α through redox regulation of mTORC2 activation and initiation of mRNA translation, Oncogene(in press) http://dx.doi.org/10.1038/ onc.2012.333 [Electronic publication ahead of print].
88. C.-H. Chen, T. Shaikenov, T.R. Peterson, R. Aimbetov, A.K. Bissenbaev, S.-W. Lee, J. Wu, H.-K. Lin, and D.D. Sarbassov ER stress inhibits mTORC2 and Akt signaling through GSK-3β-mediated phosphorylation of rictor Sci. Signal. 4 2011
89. W. Li, M. Petrimpol, K.D. Molle, M.N. Hall, E.J. Battegay, and R. Humar Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2 Circ. Res. 100 2007 79 87 (Pubitemid 46066776)
90. V.P. Krymskaya, J. Snow, G. Cesarone, I. Khavin, D.A. Goncharov, P.N. Lim, S.C. Veasey, K. Ihida-Stansbury, P.L. Jones, and E.A. Goncharova mTOR is required for pulmonary arterial vascular smooth muscle cell proliferation under chronic hypoxia FASEB J. 25 2011 1922 1933
91. J. Martin, J. Masri, A. Bernath, R.N. Nishimura, and J. Gera Hsp70 associates with Rictor and is required for mTORC2 formation and activity Biochem. Biophys. Res. Commun. 372 2008 578 583
92. J. Copp, G. Manning, and T. Hunter TORC-specific phosphorylation of mTOR: phospho-Ser2481 is a marker for intact mTORC2 Cancer Res. 69 2009 1821 1827
93. S.H. Um, F. Frigerio, M. Watanabe, F. Picard, M. Joaquin, M. Sticker, S. Fumagalli, P.R. Allegrini, S.C. Kozma, J. Auwerx, and G. Thomas Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity Nature 431 2004 200 205 (Pubitemid 39243474)
94. L.-A. Julien, A. Carriere, J. Moreau, and P.P. Roux mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulates mTORC2 signaling Mol. Cell. Biol. 30 2010 908 921
95. H.H. Zhang, A.I. Lipovsky, C.C. Dibble, M. Sahin, and B.D. Manning S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt Mol. Cell 24 2006 185 197 (Pubitemid 44574477)
96. M.K. Holz, and J. Blenis Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase J. Biol. Chem. 280 2005 26089 26093 (Pubitemid 41022201)
97. G.G. Chiang, and R.T. Abraham Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase J. Biol. Chem. 280 2005 25485 25490 (Pubitemid 40962253)
98. M. Rosner, N. Siegel, A. Valli, C. Fuchs, and M. Hengstschläger mTOR phosphorylated at S2448 binds to raptor and rictor Amino Acids 38 2010 223 228
99. D.D. Sarbassov, D.A. Guertin, S.M. Ali, and D.M. Sabatini Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex Science 307 2005 1098 1101 (Pubitemid 40262113)
100. D.A. Guertin, D.M. Stevens, C.C. Thoreen, A.A. Burds, N.Y. Kalaany, J. Moffat, M. Brown, K.J. Fitzgerald, and D.M. Sabatini 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 11 2006 859 871 (Pubitemid 44804279)
101. M. Yuan, E. Pino, L. Wu, M. Kacergis, and A.A. Soukas Identification of Akt-independent regulation of hepatic lipogenesis by mammalian target of rapamycin (mTOR) complex 2 J. Biol. Chem. 287 2012 29579 29588
102. S. Duan, J.R. Skaar, S. Kuchay, A. Toschi, N. Kanarek, Y. Ben-Neriah, and M. Pagano mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR Mol. Cell 44 2011 317 324
103. C.-H. Chen, and D.D. Sarbassov The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2 J. Biol. Chem. 286 2011 40386 40394
104. A.C. Hsieh, Y. Liu, M.P. Edlind, N.T. Ingolia, M.R. Janes, A. Sher, E.Y. Shi, C.R. Stumpf, C. Christensen, M.J. Bonham, S. Wang, P. Ren, M. Martin, K. Jessen, M.E. Feldman, J.S. Weissman, K.M. Shokat, C. Rommel, and D. Ruggero The translational landscape of mTOR signalling steers cancer initiation and metastasis Nature 485 2012 55 61
105. C.C. Thoreen, L. Chantranupong, H.R. Keys, T. Wang, N.S. Gray, and D.M. Sabatini A unifying model for mTORC1-mediated regulation of mRNA translation Nature 485 2012 109 113
106. M. Pende, S.H. Um, V. Mieulet, M. Sticker, V.L. Goss, J. Mestan, M. Mueller, S. Fumagalli, S.C. Kozma, and G. Thomas S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway Mol. Cell. Biol. 24 2004 3112 3124 (Pubitemid 38452057)
107. T. Morita, and K. Sobue Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR-p70S6K pathway J. Biol. Chem. 284 2009 27734 27745
108. V. Iadevaia, Y. Huo, Z. Zhang, L.J. Foster, and C.G. Proud Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis Biochem. Soc. Trans. 40 2012 168 172
109. C. Mayer, and I. Grummt Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases Oncogene 25 2006 6384 6391 (Pubitemid 44582283)
110. C.K. Tsang, H. Liu, and X.F.S. Zheng mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes Cell Cycle (Georgetown, Tex.) 9 2010 953 957
111. B. Shor, J. Wu, Q. Shakey, L. Toral-Barza, C. Shi, M. Follettie, and K. Yu Requirement of the mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells J. Biol. Chem. 285 2010 15380 15392
112. C. Mayer, J. Zhao, X. Yuan, and I. Grummt mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability Genes Dev. 18 2004 423 434 (Pubitemid 38316349)
113. K.M. Hannan, Y. Brandenburger, A. Jenkins, K. Sharkey, A. Cavanaugh, L. Rothblum, T. Moss, G. Poortinga, G.A. McArthur, R.B. Pearson, and R.D. Hannan mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF Mol. Cell. Biol. 23 2003 8862 8877 (Pubitemid 37433385)
114. G.A. Nader, T.J. McLoughlin, and K.A. Esser mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators Am. J. Physiol. Cell Physiol. 289 2005 C1457 1465
115. A. Woiwode, S.A. Johnson, S. Zhong, C. Zhang, R.G. Roeder, M. Teichmann, and D.L. Johnson PTEN represses RNA polymerase III-dependent transcription by targeting the TFIIIB complex Mol. Cell. Biol. 28 2008 4204 4214 (Pubitemid 351813003)
116. T. Kantidakis, B.A. Ramsbottom, J.L. Birch, S.N. Dowding, and R.J. White mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1 Proc. Natl. Acad. Sci. U.S.A. 107 2010 11823 11828
117. R.M. Marion, A. Regev, E. Segal, Y. Barash, D. Koller, N. Friedman, and E.K. O'Shea Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression Proc. Natl. Acad. Sci. U.S.A. 101 2004 14315 14322 (Pubitemid 39346746)
118. D.E. Martin, A. Soulard, and M.N. Hall TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1 Cell 119 2004 969 979 (Pubitemid 40037610)
119. H. Onda, P.B. Crino, H. Zhang, R.D. Murphey, L. Rastelli, B.E. Gould Rothberg, and D.J. Kwiatkowski Tsc2 null murine neuroepithelial cells are a model for human tuber giant cells, and show activation of an mTOR pathway Mol. Cell. Neurosci. 21 2002 561 574 (Pubitemid 36062714)
120. D.A. Guertin, K.V. Guntur, G.W. Bell, C.C. Thoreen, and D.M. Sabatini Functional genomics identifies TOR-regulated genes that control growth and division Curr. Biol. 16 2006 958 970 (Pubitemid 43728212)
121. M.E. Tyburczy, K. Kotulska, P. Pokarowski, J. Mieczkowski, J. Kucharska, W. Grajkowska, M. Roszkowski, S. Jozwiak, and B. Kaminska Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications Am. J. Pathol. 176 2010 1878 1890
122. K. Duvel, J.L. Yecies, S. Menon, P. Raman, A.I. Lipovsky, A.L. Souza, E. Triantafellow, Q. Ma, R. Gorski, S. Cleaver, M.G. Vander Heiden, J.P. MacKeigan, P.M. Finan, C.B. Clish, L.O. Murphy, and B.D. Manning Activation of a metabolic gene regulatory network downstream of mTOR complex 1 Mol. Cell 39 2010 171 183
123. S. Pena-Llopis, S. Vega-Rubin-de-Celis, J.C. Schwartz, N.C. Wolff, T.A. Tran, L. Zou, X.J. Xie, D.R. Corey, and J. Brugarolas Regulation of TFEB and V-ATPases by mTORC1 EMBO J. 30 2011 3242 3258
124. S. Li, M.S. Brown, and J.L. Goldstein Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis Proc. Natl. Acad. Sci. U.S.A. 107 2010 3441 3446
125. C.A. Lewis, B. Griffiths, C.R. Santos, M. Pende, and A. Schulze Genetic ablation of S6-kinase does not prevent processing of SREBP1 Adv. Enzym. Regul. 51 2011 280 290
126. T. Porstmann, C.R. Santos, B. Griffiths, M. Cully, M. Wu, S. Leevers, J.R. Griffiths, Y.L. Chung, and A. Schulze SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth Cell Metab. 8 2008 224 236
127. T.R. Peterson, S.S. Sengupta, T.E. Harris, A.E. Carmack, S.A. Kang, E. Balderas, D.A. Guertin, K.L. Madden, A.E. Carpenter, B.N. Finck, and D.M. Sabatini mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway Cell 146 2011 408 420
128. A. Toschi, E. Lee, N. Gadir, M. Ohh, and D.A. Foster Differential dependence of hypoxia-inducible factors 1 alpha and 2 alpha on mTORC1 and mTORC2 J. Biol. Chem. 283 2008 34495 34499
129. S.C. Land, and A.R. Tee Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif J. Biol. Chem. 282 2007 20534 20543 (Pubitemid 47100043)
130. D.B. Shackelford, D.S. Vasquez, J. Corbeil, S. Wu, M. Leblanc, C.-L. Wu, D.R. Vera, and R.J. Shaw mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndrome Proc. Natl. Acad. Sci. U.S.A. 106 2009 11137 11142
131. J. Yu, J. Li, S. Zhang, X. Xu, M. Zheng, G. Jiang, and F. Li IGF-1 induces hypoxia-inducible factor 1α-mediated GLUT3 expression through PI3K/Akt/mTOR dependent pathways in PC12 cells Brain Res. 1430 2012 18 24
132. C.D. Befani, P.J. Vlachostergios, E. Hatzidaki, A. Patrikidou, S. Bonanou, G. Simos, C.N. Papandreou, and P. Liakos Bortezomib represses HIF-1alpha protein expression and nuclear accumulation by inhibiting both PI3K/Akt/TOR and MAPK pathways in prostate cancer cells J. Mol. Med.(Berl.) 90 2012 45 54
133. M.F. McCarty, J. Barroso-Aranda, and F. Contreras Practical strategies for suppressing hypoxia-inducible factor activity in cancer therapy Med. Hypotheses 74 2010 789 797
134. K. Matsumoto, T. Arao, K. Tanaka, H. Kaneda, K. Kudo, Y. Fujita, D. Tamura, K. Aomatsu, T. Tamura, Y. Yamada, N. Saijo, and K. Nishio mTOR signal and hypoxia-inducible factor-1 alpha regulate CD133 expression in cancer cells Cancer Res. 69 2009 7160 7164
135. K. Nakamura, F. Tan, Z. Li, and C.J. Thiele NGF activation of TrkA induces vascular endothelial growth factor expression via induction of hypoxia-inducible factor-1alpha Mol. Cell. Neurosci. 46 2011 498 506
136. J.T. Cunningham, J.T. Rodgers, D.H. Arlow, F. Vazquez, V.K. Mootha, and P. Puigserver mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex Nature 450 2007 736 740 (Pubitemid 350207689)
137. S.M. Blattler, F. Verdeguer, M. Liesa, J.T. Cunningham, R.O. Vogel, H. Chim, H. Liu, K. Romanino, O.S. Shirihai, F. Vazquez, M.A. Ruegg, Y. Shi, and P. Puigserver Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle Mol. Cell. Biol. 32 2012 3333 3346
138. A. Roczniak-Ferguson, C.S. Petit, F. Froehlich, S. Qian, J. Ky, B. Angarola, T.C. Walther, and S.M. Ferguson The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis Sci. Signal. 5 2012
139. C. Settembre, R. Zoncu, D.L. Medina, F. Vetrini, S. Erdin, S. Erdin, T. Huynh, M. Ferron, G. Karsenty, M.C. Vellard, V. Facchinetti, D.M. Sabatini, and A. Ballabio A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB EMBO J. 31 2012 1095 1108
140. J.A. Martina, Y. Chen, M. Gucek, and R. Puertollano MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB Autophagy 8 2012 903 914
141. M.C. Ortells, B. Morancho, K. Drews-Elger, B. Viollet, K.R. Laderoute, C. Lopez-Rodriguez, and J. Aramburu Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin Nucleic Acids Res. 40 2012 4368 4384
142. V. Iadevaia, Z. Zhang, E. Jan, and C.G. Proud mTOR signaling regulates the processing of pre-rRNA in human cells Nucleic Acids Res. 40 2012 2527 2539
143. A. Vazquez-Martin, S. Cufi, C. Oliveras-Ferraros, and J.A. Menendez Raptor, a positive regulatory subunit of mTOR complex 1, is a novel phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal nucleolus organizer regions (NORs) Cell Cycle (Georgetown, Tex.) 10 2011 3140 3152
144. K.T. Pfaffenbach, A.M. Nivala, L. Reese, F. Ellis, D. Wang, Y. Wei, and M.J. Pagliassotti Rapamycin inhibits postprandial-mediated X-box-binding protein-1 splicing in rat liver J. Nutr. 140 2010 879 884
145. E.S. White, R.L. Sagana, A.J. Booth, M. Yan, A.M. Cornett, C.A. Bloomheart, J.L. Tsui, C.A. Wilke, B.B. Moore, J.D. Ritzenthaler, J. Roman, and A.F. Muro Control of fibroblast fibronectin expression and alternative splicing via the PI3K/Akt/mTOR pathway Exp. Cell Res. 316 2010 2644 2653
146. E.T. Goh, O.E. Pardo, N. Michael, A. Niewiarowski, N. Totty, D. Volkova, I.R. Tsaneva, M.J. Seckl, and I. Gout Involvement of heterogeneous ribonucleoprotein F in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway J. Biol. Chem. 285 2010 17065 17076
147. S.P. Han, Y.H. Tang, and R. Smith Functional diversity of the hnRNPs: past, present and perspectives Biochem. J. 430 2010 379 392
148. P.P. Hsu, S.A. Kang, J. Rameseder, Y. Zhang, K.A. Ottina, D. Lim, T.R. Peterson, Y. Choi, N.S. Gray, M.B. Yaffe, J.A. Marto, and D.M. Sabatini The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling Science 332 2011 1317 1322
149. M. Hamada, A. Haeger, K.B. Jeganathan, J.H. van Ree, L. Malureanu, S. Walde, J. Joseph, R.H. Kehlenbach, and J.M. van Deursen Ran-dependent docking of importin-beta to RanBP2/Nup358 filaments is essential for protein import and cell viability J. Cell Biol. 194 2011 597 612
150. N. Dai, J. Rapley, M. Angel, M.F. Yanik, M.D. Blower, and J. Avruch mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry Genes Dev. 25 2011 1159 1172
151. M. Perycz, A.S. Urbanska, P.S. Krawczyk, K. Parobczak, and J. Jaworski Zipcode binding protein 1 regulates the development of dendritic arbors in hippocampal neurons J. Neurosci. 31 2011 5271 5285
152. T. Eom, L.N. Antar, R.H. Singer, and G.J. Bassell Localization of a beta-actin messenger ribonucleoprotein complex with zipcode-binding protein modulates the density of dendritic filopodia and filopodial synapses J. Neurosci. 23 2003 10433 10444 (Pubitemid 37444620)
153. H.L. Zhang, T. Eom, Y. Oleynikov, S.M. Shenoy, D.A. Liebelt, J.B. Dictenberg, R.H. Singer, and G.J. Bassell Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility Neuron 31 2001 261 275 (Pubitemid 32762979)
154. Y. Yu, S.O. Yoon, G. Poulogiannis, Q. Yang, X.M. Ma, J. Villen, N. Kubica, G.R. Hoffman, L.C. Cantley, S.P. Gygi, and J. Blenis Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling Science 332 2011 1322 1326
155. M. Baou, A. Jewell, and J.J. Murphy TIS11 family proteins and their roles in posttranscriptional gene regulation J. Biomed. Biotechnol. 2009 2009 634520
156. M. Schmidlin, M. Lu, S.A. Leuenberger, G. Stoecklin, M. Mallaun, B. Gross, R. Gherzi, D. Hess, B.A. Hemmings, and C. Moroni The ARE-dependent mRNA-destabilizing activity of BRF1 is regulated by protein kinase B EMBO J. 23 2004 4760 4769 (Pubitemid 40069706)
157. M. Bayeva, A. Khechaduri, S. Puig, H.C. Chang, S. Patial, P.J. Blackshear, and H. Ardehali mTOR regulates cellular iron homeostasis through tristetraprolin Cell Metab. 16 2012 645 657
158. A. Schmidt, J. Kunz, and M.N. Hall TOR2 is required for organization of the actin cytoskeleton in yeast Proc. Natl. Acad. Sci. U.S.A. 93 1996 13780 13785 (Pubitemid 26424197)
159. A. Schmidt, M. Bickle, T. Beck, and M.N. Hall The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2 Cell 88 1997 531 542 (Pubitemid 27154418)
160. J.H. Choi, N.R. Adames, T.F. Chan, C. Zeng, J.A. Cooper, and X.F. Zheng TOR signaling regulates microtubule structure and function Curr. Biol. 10 2000 861 864 (Pubitemid 30597207)
161. A. Akhmanova, and C.C. Hoogenraad Microtubule plus-end-tracking proteins: mechanisms and functions Curr. Opin. Cell Biol. 17 2005 47 54 (Pubitemid 40138087)
162. J. Jaworski, C.C. Hoogenraad, and A. Akhmanova Microtubule plus-end tracking proteins in differentiated mammalian cells Int. J. Biochem. Cell Biol. 40 2008 619 637 (Pubitemid 351288598)
163. G. Lansbergen, and A. Akhmanova Microtubule plus end: a hub of cellular activities Traffic 7 2006 499 507 (Pubitemid 44026748)
164. L.T. Tran, R.W. Wang'ondu, J.B. Weng, G.W. Wanjiku, C.M. Fong, A.C. Kile, D.M. Koepp, and J.K. Hood-DeGrenier TORC1 kinase and the S-phase cyclin Clb5 collaborate to promote mitotic spindle assembly and DNA replication in S. cerevisiae Curr. Genet. 56 2010 479 493
165. J.H. Choi, P.G. Bertram, R. Drenan, J. Carvalho, H.H. Zhou, and X.F. Zheng The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase EMBO Rep. 3 2002 988 994 (Pubitemid 35256474)
166. L. Swiech, M. Blazejczyk, M. Urbanska, P. Pietruszka, B.R. Dortland, A.R. Malik, P.S. Wulf, C.C. Hoogenraad, and J. Jaworski CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology J. Neurosci. 31 2011 4555 4568
167. X. Jiang, and R.S. Yeung Regulation of microtubule-dependent protein transport by the TSC2/mammalian target of rapamycin pathway Cancer Res. 66 2006 5258 5269 (Pubitemid 43844950)
168. J. Jaworski, S. Spangler, D.P. Seeburg, C.C. Hoogenraad, and M. Sheng Control of dendritic arborization by the phosphoinositide-3′-kinase-Akt- mammalian target of rapamycin pathway J. Neurosci. 25 2005 11300 11312 (Pubitemid 43083704)
169. X. Jiang, H. Kenerson, L. Aicher, R. Miyaoka, J. Eary, J. Bissler, and R.S. Yeung The tuberous sclerosis complex regulates trafficking of glucose transporters and glucose uptake Am. J. Pathol. 172 2008 1748 1756 (Pubitemid 351793365)
170. L. Yu, C.K. McPhee, L. Zheng, G.A. Mardones, Y. Rong, J. Peng, N. Mi, Y. Zhao, Z. Liu, F. Wan, D.W. Hailey, V. Oorschot, J. Klumperman, E.H. Baehrecke, and M.J. Lenardo Termination of autophagy and reformation of lysosomes regulated by mTOR Nature 465 2010 942 946
171. L. Liu, S. Das, W. Losert, and C.A. Parent mTORC2 regulates neutrophil chemotaxis in a cAMP- and RhoA-dependent fashion Dev. Cell 19 2010 845 857
172. H. Murata, M. Sakaguchi, Y. Jin, Y. Sakaguchi, J.-i. Futami, H. Yamada, K. Kataoka, and N.-h. Huh A new cytosolic pathway from a Parkinson disease-associated kinase, BRPK/PINK1: activation of AKT via mTORC2 J. Biol. Chem. 286 2011 7182 7189
173. F. Zhang, X. Zhang, M. Li, P. Chen, B. Zhang, H. Guo, W. Cao, X. Wei, X. Cao, X. Hao, and N. Zhang mTOR complex component Rictor interacts with PKCzeta and regulates cancer cell metastasis Cancer Res. 70 2010 9360 9370
174. S. Dada, N. Demartines, and O. Dormond mTORC2 regulates PGE2-mediated endothelial cell survival and migration Biochem. Biophys. Res. Commun. 372 2008 875 879
175. L. Liu, Y. Luo, L. Chen, T. Shen, B. Xu, W. Chen, H. Zhou, X. Han, and S. Huang Rapamycin inhibits cytoskeleton reorganization and cell motility by suppressing RhoA expression and activity J. Biol. Chem. 285 2010 38362 38373
176. S.C. Moss, D.J. Lightell Jr., S.O. Marx, A.R. Marks, and T.C. Woods Rapamycin regulates endothelial cell migration through regulation of the cyclin-dependent kinase inhibitor p27Kip1 J. Biol. Chem. 285 2010 11991 11997
177. I. Hernández-Negrete, J. Carretero-Ortega, H. Rosenfeldt, R. Hernández-García, J.V. Calderón-Salinas, G. Reyes-Cruz, J.S. Gutkind, and J. Vázquez-Prado P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration J. Biol. Chem. 282 2007 23708 23715 (Pubitemid 47311970)
178. N.K. Agarwal, C.H. Chen, H. Cho, D.R. Boulbès, E. Spooner, D.D. Sarbassov, Rictor regulates cell migration by suppressing RhoGDI2, Oncogene (in press) http://dx.doi.org/10.1038/onc.2012.297. [Electronic publication ahead of print].
179. L. Liu, L. Chen, J. Chung, and S. Huang Rapamycin inhibits F-actin reorganization and phosphorylation of focal adhesion proteins Oncogene 27 2008 4998 5010
180. N. Mizushima Autophagy: process and function Genes Dev. 21 2007 2861 2873 (Pubitemid 350133435)
181. N. Hosokawa, T. Hara, T. Kaizuka, C. Kishi, A. Takamura, Y. Miura, S. Iemura, T. Natsume, K. Takehana, N. Yamada, J.L. Guan, N. Oshiro, and N. Mizushima Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy Mol. Biol. Cell 20 2009 1981 1991
182. C.H. Jung, C.B. Jun, S.H. Ro, Y.M. Kim, N.M. Otto, J. Cao, M. Kundu, and D.H. Kim ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery Mol. Biol. Cell 20 2009 1992 2003
183. I.G. Ganley, H. Lam du, J. Wang, X. Ding, S. Chen, and X. Jiang ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy J. Biol. Chem. 284 2009 12297 12305
184. I. Koren, E. Reem, and A. Kimchi DAP1, a novel substrate of mTOR, negatively regulates autophagy Curr. Biol. 20 2010 1093 1098
185. I. Koren, E. Reem, and A. Kimchi Autophagy gets a brake: DAP1, a novel mTOR substrate, is activated to suppress the autophagic process Autophagy 6 2010 1179 1180
186. T. Galvez, M.N. Teruel, W.D. Heo, J.T. Jones, M.L. Kim, J. Liou, J.W. Myers, and T. Meyer siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake Genome Biol. 8 2007 R142
187. L. Pelkmans, E. Fava, H. Grabner, M. Hannus, B. Habermann, E. Krausz, and M. Zerial Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis Nature 436 2005 78 86 (Pubitemid 40966188)
188. K.M. Hennig, J. Colombani, and T.P. Neufeld TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth J. Cell Biol. 173 2006 963 974
189. F.J. Rosario, N. Jansson, Y. Kanai, P.D. Prasad, T.L. Powell, and T. Jansson Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters Endocrinology 152 2011 1119 1129
190. S. Roos, O. Lagerlof, M. Wennergren, T.L. Powell, and T. Jansson Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling Am. J. Physiol. Cell Physiol. 297 2009 C723 731
191. A. Almilaji, T. Pakladok, A. Guo, C. Munoz, M. Föller, and F. Lang Regulation of the glutamate transporter EAAT3 by mammalian target of rapamycin mTOR Biochem. Biophys. Res. Commun. 421 2012 159 163
192. E. Kleymenova, O. Ibraghimov-Beskrovnaya, H. Kugoh, J. Everitt, H. Xu, K. Kiguchi, G. Landes, P. Harris, and C. Walker Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene Mol. Cell 7 2001 823 832 (Pubitemid 32436442)
193. H. Kugoh, E. Kleymenova, and C.L. Walker Retention of membrane-localized beta-catenin in cells lacking functional polycystin-1 and tuberin Mol. Carcinog. 33 2002 131 136 (Pubitemid 34195193)
194. K.A. Jones, X. Jiang, Y. Yamamoto, and R.S. Yeung Tuberin is a component of lipid rafts and mediates caveolin-1 localization: role of TSC2 in post-Golgi transport Exp. Cell Res. 295 2004 512 524 (Pubitemid 38490503)
195. G. Panasyuk, I. Nemazanyy, A. Zhyvoloup, V. Filonenko, D. Davies, M. Robson, R.B. Pedley, M. Waterfield, and I. Gout mTORbeta splicing isoform promotes cell proliferation and tumorigenesis J. Biol. Chem. 284 2009 30807 30814