Amino acid signalling upstream of mTOR (original) (raw)

• Laplante, M. & Sabatini, D. M. mTOR signaling in growth control and disease. Cell 149, 274–293 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Zoncu, R., Efeyan, A. & Sabatini, D. M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nature Rev. Mol. Cell Biol. 12, 21–35 (2011).
  Article CAS Google Scholar
• Inoki, K. et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell 126, 955–968 (2006).
  Article CAS PubMed Google Scholar
• Gwinn, D. M. et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 30, 214–226 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Sancak, Y. et al. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320, 1496–1501 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Hara, K. et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273, 14484–14494 (1998).
  Article CAS PubMed Google Scholar
• Wang, X., Campbell, L. E., Miller, C. M. & Proud, C. G. Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem. J. 334, 261–267 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Bauchart-Thevret, C., Cui, L., Wu, G. & Burrin, D. G. Arginine-induced stimulation of protein synthesis and survival in IPEC-J2 cells is mediated by mTOR but not nitric oxide. Am. J. Physiol. Endocrinol. Metab. 299, e899–e909 (2010).
  Article CAS PubMed Google Scholar
• Nicklin, P. et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 136, 521–534 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Duran, R. V. et al. Glutaminolysis activates Rag–mTORC1 signaling. Mol. Cell 47, 349–358 (2012).
  Article CAS PubMed Google Scholar
• van der Vos, K. E. & Coffer, P. J. Glutamine metabolism links growth factor signaling to the regulation of autophagy. Autophagy 8, 1862–1864 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• van der Vos, K. E. et al. Modulation of glutamine metabolism by the PI(3)K–PKB–FOXO network regulates autophagy. Nature Cell Biol. 14, 829–837 (2012).
  Article CAS PubMed Google Scholar
• Smith, E. M., Finn, S. G., Tee, A. R., Browne, G. J. & Proud, C. G. 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, 18717–18727 (2005).
  Article CAS PubMed Google Scholar
• 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. 280, 23433–23436 (2005).
  Article CAS PubMed Google Scholar
• Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P. & Guan, K. L. Regulation of TORC1 by Rag GTPases in nutrient response. Nature Cell Biol. 10, 935–945 (2008).
  Article CAS PubMed Google Scholar
• Nakashima, N., Noguchi, E. & Nishimoto, T. Saccharomyces cerevisiae putative G protein, Gtr1p, which forms complexes with itself and a novel protein designated as Gtr2p, negatively regulates the Ran/Gsp1p G protein cycle through Gtr2p. Genetics 152, 853–867 (1999).
  CAS PubMed PubMed Central Google Scholar
• Sekiguchi, T. et al. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J. Biol. Chem. 276, 7246–7257 (2001).
  Article CAS PubMed Google Scholar
• Gong, R. et al. Crystal structure of the Gtr1p–Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation. Genes Dev. 25, 1668–1673 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Jeong, J. H. et al. Crystal structure of the Gtr1pGTP–Gtr2pGDP protein complex reveals large structural rearrangements triggered by GTP-to-GDP conversion. J. Biol. Chem. 287, 29648–29653 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Sancak, Y. et al. Ragulator–Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141, 290–303 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• De Virgilio, C. & Loewith, R. Cell growth control: little eukaryotes make big contributions. Oncogene 25, 6392–6415 (2006).
  Article CAS PubMed Google Scholar
• Binda, M. et al. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol. Cell 35, 563–573 (2009).
  Article CAS PubMed Google Scholar
• Li, L. et al. Regulation of mTORC1 by the Rab and Arf GTPases. J. Biol. Chem. 285, 19705–19709 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Bar-Peled, L., Schweitzer, L. D., Zoncu, R. & Sabatini, D. M. Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1. Cell 150, 1196–1208 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Ashrafi, K., Farazi, T. A. & Gordon, J. I. A role for Saccharomyces cerevisiae fatty acid activation protein 4 in regulating protein _N_-myristoylation during entry into stationary phase. J. Biol. Chem. 273, 25864–25874 (1998).
  Article CAS PubMed Google Scholar
• Kogan, K., Spear, E. D., Kaiser, C. A. & Fass, D. Structural conservation of components in the amino acid sensing branch of the TOR pathway in yeast and mammals. J. Mol. Biol. 402, 388–398 (2010).
  Article CAS PubMed Google Scholar
• Loewith, R. & Hall, M. N. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 189, 1177–1201 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, T., Peli-Gulli, M. P., Yang, H., De Virgilio, C. & Ding, J. Ego3 functions as a homodimer to mediate the interaction between Gtr1–Gtr2 and Ego1 in the EGO complex to activate TORC1. Structure 20, 2151–2160 (2012).
  Article CAS PubMed Google Scholar
• Garcia-Saez, I., Lacroix, F. B., Blot, D., Gabel, F. & Skoufias, D. A. Structural characterization of HBXIP: the protein that interacts with the anti-apoptotic protein survivin and the oncogenic viral protein HBx. J. Mol. Biol. 405, 331–340 (2011).
  Article CAS PubMed Google Scholar
• Kurzbauer, R. et al. Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes. Proc. Natl Acad. Sci. USA 101, 10984–10989 (2004).
  Article CAS PubMed PubMed Central Google Scholar
• Lunin, V. V. et al. The structure of the MAPK scaffold, MP1, bound to its partner, p14. A complex with a critical role in endosomal map kinase signaling. J. Biol. Chem. 279, 23422–23430 (2004).
  Article CAS PubMed Google Scholar
• Valbuena, N., Guan, K. L. & Moreno, S. The Vam6–Gtr1/Gtr2 pathway activates TORC1 in response to amino acids in fission yeast. J. Cell Sci. 125, 1920–1928 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Messler, S. et al. The TGF-β signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development. Immunobiology 216, 343–350 (2011).
  Article CAS PubMed Google Scholar
• Zoncu, R. et al. mTORC1 senses lysosomal amino acids through an inside–out mechanism that requires the vacuolar H+-ATPase. Science 334, 678–683 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Nishi, T. & Forgac, M. The vacuolar (H+)-ATPases — nature's most versatile proton pumps. Nature Rev. Mol. Cell Biol. 3, 94–103 (2002).
  Article CAS Google Scholar
• Fonseca, B. D. et al. Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling. J. Biol. Chem. 287, 17530–17545 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Balgi, A. D. et al. Regulation of mTORC1 signaling by pH. PLoS ONE 6, e21549 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Han, J. M. et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149, 410–424 (2012).
  Article CAS PubMed Google Scholar
• Bonfils, G. et al. Leucyl-tRNA synthetase controls TORC1 via the EGO complex. Mol. Cell 46, 105–110 (2012).
  Article CAS PubMed Google Scholar
• Avruch, J. et al. Amino acid regulation of TOR complex 1. Am. J. Physiol. Endocrinol. Metab. 296, e592–e602 (2009).
  Article CAS PubMed Google Scholar
• Kim, Y. M. et al. SH3BP4 is a negative regulator of amino acid–Rag GTPase–mTORC1 signaling. Mol. Cell 46, 833–846 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Mizushima, N. & Komatsu, M. Autophagy: renovation of cells and tissues. Cell 147, 728–741 (2011).
  Article CAS PubMed Google Scholar
• Mizushima, N. & Klionsky, D. J. Protein turnover via autophagy: implications for metabolism. Annu. Rev. Nutr. 27, 19–40 (2007).
  Article CAS PubMed Google Scholar
• Kim, J., Kundu, M., Viollet, B. & Guan, K. L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biol. 13, 132–141 (2011).
  Article CAS PubMed Google Scholar
• Ganley, I. G. et al. ULK1·ATG13·FIP200 complex mediates mTOR signaling and is essential for autophagy. J. Biol. Chem. 284, 12297–12305 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Hosokawa, N. et al. Nutrient-dependent mTORC1 association with the ULK1–Atg13–FIP200 complex required for autophagy. Mol. Biol. Cell 20, 1981–1991 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Jung, C. H. et al. ULK–Atg13–FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 20, 1992–2003 (2009).
  CAS PubMed PubMed Central Google Scholar
• Martina, J. A., Chen, Y., Gucek, M. & Puertollano, R. mTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB. Autophagy 8, 903–914 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Settembre, C. et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31, 1095–1108 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Orlova, M., Kanter, E., Krakovich, D. & Kuchin, S. Nitrogen availability and TOR regulate the Snf1 protein kinase in Saccharomyces cerevisiae. Eukaryot. Cell 5, 1831–1837 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, Z., Wilson, W. A., Fujino, M. A. & Roach, P. J. Antagonistic controls of autophagy and glycogen accumulation by Snf1p, the yeast homolog of AMP-activated protein kinase, and the cyclin-dependent kinase Pho85p. Mol. Cell. Biol. 21, 5742–5752 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Hirose, E., Nakashima, N., Sekiguchi, T. & Nishimoto, T. RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1–GTPase pathway. J. Cell Sci. 111, 11–21 (1998).
  CAS PubMed Google Scholar
• Nakashima, N., Noguchi, E. & Nishimoto, T. Saccharomyces cerevisiae putative G protein, Gtr1p, which forms complexes with itself and a novel protein designated as Gtr2p, negatively regulates the Ran/Gsp1p G protein cycle through Gtr2p. Genetics 152, 853–867 (1999).
  CAS PubMed PubMed Central Google Scholar