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Amino acid signalling upstream of mTOR
Open accessAbstract
Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that is part of mTOR complex 1 (mTORC1), a master regulator that couples amino acid availability to cell growth and autophagy. Multiple cues modulate mTORC1 activity, such as growth factors, stress, energy status and amino acids. Although amino acids are key environmental stimuli, exactly how they are sensed and how they activate mTORC1 is not fully understood. Recently, a model has emerged whereby mTORC1 activation occurs at the lysosome and is mediated through an amino acid sensing cascade involving RAG GTPases, Ragulator and vacuolar H(+)-ATPase (v-ATPase).
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“In contrast, all other signalling components are present for regulation of mTORC1, depending on physiologic demands such as energy deprivation sensing29 and amino acid sensing30.”
From Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein (2016) · cites this paper as [30]
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Cites
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Self-citationAutophagy: Renovation of Cells and Tissues
Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,615
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773
Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A. L., Nada, S., & Sabatini, D. M. (2010) · Cell · doi:10.1016/j.cell.2010.02.024 · Cited by 2,464
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076
ULK-Atg13-FIP200 Complexes Mediate mTOR Signaling to the Autophagy Machinery
Jung, C. H., Jun, C. B., Ro, S.-H., Kim, Y.-M., Otto, N. M., Cao, J., Kundu, M., & Kim, D.-H. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1249 · Cited by 2,025
A lysosome‐to‐nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB
Settembre, C., Zoncu, R., Medina, D. L., Vetrini, F., Erdin, S., Erdin, S., Huynh, T., Ferron, M., Karsenty, G., Vellard, M. C., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.32 · Cited by 1,920
Bidirectional Transport of Amino Acids Regulates mTOR and Autophagy
Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., et al. (2009) · Cell · doi:10.1016/j.cell.2008.11.044 · Cited by 1,798
Zoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673
ULK1·ATG13·FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy
Ganley, I. G., Lam, D. H., Wang, J., Ding, X., Chen, S., & Jiang, X. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900573200 · Cited by 1,447
Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.055 · Cited by 1,377
Self-citationHara, K., Yonezawa, K., Weng, Q.-P., Kozlowski, M. T., BELHAM, C. M., & Avruch, J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14484 · Cited by 1,370
Regulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349
Self-citationMTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB
Martina, J. A., Chen, Y., Gucek, M., & Puertollano, R. (2012) · Autophagy · doi:10.4161/auto.19653 · Cited by 1,333
The vacuolar (H+)-ATPases — nature's most versatile proton pumps
Nishi, T., & Forgac, M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm729 · Cited by 1,197
Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control
Loewith, R., & Hall, M. N. (2011) · Genetics · doi:10.1534/genetics.111.133363 · Cited by 927
Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1
Bar-Peled, L., Schweitzer, L. D., Zoncu, R., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.07.032 · Cited by 918
Leucyl-tRNA Synthetase Is an Intracellular Leucine Sensor for the mTORC1-Signaling Pathway
Han, J. M., Jeong, S. J., Park, M. C., Kim, G., Kwon, N. H., Kim, H. K., Ha, S. H., Ryu, S. H., & Kim, S. (2012) · Cell · doi:10.1016/j.cell.2012.02.044 · Cited by 824
Protein Turnover Via Autophagy: Implications for Metabolism
Mizushima, N., & Klionsky, D. J. (2007) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.27.061406.093749 · Cited by 813
Glutaminolysis Activates Rag-mTORC1 Signaling
Durán, R. V., Oppliger, W., Robitaille, A. M., Heiserich, L., Skendaj, R., Gottlieb, E., & Hall, M. N. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.05.043 · Cited by 766
The Vam6 GEF Controls TORC1 by Activating the EGO Complex
Binda, M., Gulli, M., Bonfils, G., Panchaud, N., Urban, J., Sturgill, T. W., Loewith, R., & VIRGILIO, C. D. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.06.033 · Cited by 432
Amino acid regulation of TOR complex 1
Avruch, J., Long, X., Ortiz-Vega, S., Rapley, J., Papageorgiou, A., & Dai, N. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90645.2008 · Cited by 400
Smith, E. M., FINN, S. G., Tee, A. R., Browne, G. J., & Proud, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414499200 · Cited by 354
Rheb Binding to Mammalian Target of Rapamycin (mTOR) Is Regulated by Amino Acid Sufficiency
Long, X., Ortiz-Vega, S., Lin, Y., & Avruch, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500169200 · Cited by 349
Amino acid availability regulates p70 S6 kinase and multiple translation factors
Wang, X., Campbell, L., Miller, C. M., & Proud, C. G. (1998) · Biochemical Journal · doi:10.1042/bj3340261 · Cited by 341
Leucyl-tRNA Synthetase Controls TORC1 via the EGO Complex
Bonfils, G., Jaquenoud, M., Bontron, S., Ostrowicz, C. W., Ungermann, C., & VIRGILIO, C. D. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.02.009 · Cited by 338
Wang, Z., Wilson, W. A., Fujino, M., & Roach, P. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.17.5742-5752.2001 · Cited by 300
Modulation of glutamine metabolism by the PI(3)K–PKB–FOXO network regulates autophagy
van der Vos, K. E., Eliasson, P., Proikas‐Cezanne, T., Vervoort, S. J., van Boxtel, R., Putker, M., van Zutphen, I. J., Mauthe, M., Zellmer, S., Pals, C. E. G. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2536 · Cited by 253
Novel G Proteins, Rag C and Rag D, Interact with GTP-binding Proteins, Rag A and Rag B*
Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M., & Nishimoto, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004389200 · Cited by 249
Cell growth control: little eukaryotes make big contributions
VIRGILIO, C. D., & Loewith, R. (2006) · Oncogene · doi:10.1038/sj.onc.1209884 · Cited by 224
Fonseca, B. D., Diering, G. H., Bidinosti, M., Dalal, K., Alain, T., Balgi, A. D., Forestieri, R., Nodwell, M., Rajadurai, C. V., Gunaratnam, C., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.359638 · Cited by 160
Regulation of mTORC1 by the Rab and Arf GTPases
Li, L., Kim, E., Yuan, H., Inoki, K., Goraksha-Hicks, P., Schiesher, R. L., Neufeld, T. P., & Guan, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.c110.102483 · Cited by 153
Self-citationRegulation of mTORC1 Signaling by pH
Balgi, A. D., Diering, G. H., Donohue, E., Lam, K., Fonseca, B. D., Zimmerman, C., Numata, M., & Roberge, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021549 · Cited by 120
Nakashima, N., Noguchi, E., & Nishimoto, T. (1999) · Genetics · doi:10.1093/genetics/152.3.853 · Cited by 102
Ashrafi, K., Farazi, T. A., & Gordon, J. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.40.25864 · Cited by 99
Gong, R., Li, L., Liu, Y., Wang, P., Yang, H., Wang, L., Cheng, J., Guan, K.-L., & Xu, Y. (2011) · Genes & Development · doi:10.1101/gad.16968011 · Cited by 98
Self-citationKurzbauer, R., Teis, D., de Araujo, M. E. G., Maurer-Stroh, S., Eisenhaber, F., Bourenkov, G. P., Bartunik, H. D., Hekman, M., Rapp, U. R., Huber, L. A., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403435101 · Cited by 95
Bauchart‐Thevret, C., Cui, L., Wu, G., & Burrin, D. G. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00068.2010 · Cited by 91
RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway
Hirose, E., Nakashima, N., Sekiguchi, T., & Nishimoto, T. (1998) · Journal of Cell Science · doi:10.1242/jcs.111.1.11 · Cited by 89
SH3BP4 Is a Negative Regulator of Amino Acid-Rag GTPase-mTORC1 Signaling
Kim, Y.-M., Stone, M., Hwang, T. H., Kim, Y.-G., Dunlevy, J. R., Griffin, T. J., & Kim, D.-H. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.007 · Cited by 88
Nitrogen Availability and TOR Regulate the Snf1 Protein Kinase in Saccharomyces cerevisiae
Orlova, M., Kanter, E., Krakovich, D., & Kuchin, S. (2006) · Eukaryotic Cell · doi:10.1128/ec.00110-06 · Cited by 86
Jeong, J.-H., Lee, K.-H., Kim, Y.-M., Kim, D.-H., Oh, B.-H., & Kim, Y.-G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.c112.384420 · Cited by 68
The Structure of the MAPK Scaffold, MP1, Bound to Its Partner, p14
Lunin, V. V., Munger, C., Wagner, J., Ye, Z., Cygler, M., & Sacher, M. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401648200 · Cited by 67
Zhang, T., Gulli, M., Yang, H., VIRGILIO, C. D., & Ding, J. (2012) · Structure · doi:10.1016/j.str.2012.09.019 · Cited by 63
The Vam6-Gtr1/Gtr2 pathway activates TORC1 in response to amino acids in fission yeast
Valbuena, N., Guan, K., & Moreno, S. (2012) · Journal of Cell Science · doi:10.1242/jcs.094219 · Cited by 59
Self-citationGlutamine metabolism links growth factor signaling to the regulation of autophagy
van der Vos, K. E., & Coffer, P. J. (2012) · Autophagy · doi:10.4161/auto.22152 · Cited by 58
Kogan, K., Spear, E. D., Kaiser, C. A., & Fass, D. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.07.034 · Cited by 56
Messler, S., Kropp, S., Episkopou, V., Felici, A., Wuerthner, J., Lemke, R., Jerabek‐Willemsen, M., Willecke, R., Scheu, S., Pfeffer, K., et al. (2010) · Immunobiology · doi:10.1016/j.imbio.2010.07.006 · Cited by 37
Garcia-Saez, I., Lacroix, F., Blot, D., Gabel, F., & Skoufias, D. A. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.10.046 · Cited by 36
Research works printed but not linked: 1
- 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). · DOI
Cited by
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Kim, Y. C., & Guan, K.-L. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73939 · Cited by 2,126
Self-citationAutophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585
Making new contacts: the mTOR network in metabolism and signalling crosstalk
Shimobayashi, M., & Hall, M. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3757 · Cited by 1,053
Autophagy—a key player in cellular and body metabolism
Kim, K. H., & Lee, M. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.35 · Cited by 972
Nakaya, M., Xiao, Y., Zhou, X., Chang, J., Chang, M., Cheng, X., Blonska, M., Lin, X., & Sun, S. (2014) · Immunity · doi:10.1016/j.immuni.2014.04.007 · Cited by 902
Metadata
- Authors
- Jewell, J. L., Russell, R. C., & Guan, K.-L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Guan, Kun-Liang
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2013-01-30
- Volume
- 14
- Issue
- 3
- Pages
- 133-139
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC3988467
- OpenAlex
- W2032189193
- Cited by
- 894
- References
- 52
- Citations by year
- 2026: 41 · 2025: 52 · 2024: 46 · 2023: 47 · 2022: 61 · 2021: 76 · 2020: 67 · 2019: 65 · 2018: 74 · 2017: 69 · 2016: 89 · 2015: 103 · 2014: 61 · 2013: 43
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute for Health and Care Research
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute (CA108941, R01CA108941, T32CA121938)
- National Institute of General Medical Sciences (R01GM051586)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- amino acid signalling, mTORC1, Rag GTPases, Ragulator complex, V-ATPase, lysosomes, leucyl-tRNA synthetase, amino acid sensing, autophagy, cell growth, Ser/Thr kinase
- MeSH terms
- Ras Homolog Enriched in Brain Protein, Mechanistic Target of Rapamycin Complex 1, Amino Acids, Animals, Autophagy, Humans, Leucine-tRNA Ligase, Lysosomes, Models, Biological, Neuropeptides, Proteins, Signal Transduction, Monomeric GTP-Binding Proteins, Multiprotein Complexes, Cell Proliferation, TOR Serine-Threonine Kinases
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