Amino acid signalling upstream of mTOR

Jewell, Jenna L.; Russell, Ryan C.; Guan, Kun-Liang

doi:10.1038/nrm3522

Cited by 905PI3K/AKT/mTOR signaling in cancerAutophagy in Disease and TherapyMetabolism, Diabetes, and Cancer

Amino acid signalling upstream of mTOR

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Jewell, Jenna L., Russell, Ryan C., Guan, Kun-Liang·2013·Nature Reviews Molecular Cell Biology

DOI 10.1038/nrm3522PMC PMC3988467

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Abstract

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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All other signalling components for regulation of mTORC1 depending on energy deprivation sensing and amino acid sensing are present in the tardigrade.
“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]
The Abstract describes amino-acid sensing of mTORC1 through RAG GTPases, Ragulator and v-ATPase, supporting the pathway attributed to citation 30. The review does not establish that all those signalling components are present in tardigrades; that organism-specific assertion goes beyond the cited paper. (LLM, conf=0.84)
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[53]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 10388807 PMC1460653

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Authors: Jewell, J. L., Russell, R. C., & Guan, K.-L.
Affiliations: University of California San Diego (US)
Corresponding author: Guan, Kun-Liang
ORCID: Jewell, Jenna L.
Russell, Ryan C.
Guan, Kun-Liang
Venue: Nature Reviews Molecular Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2013-01-30
Volume: 14
Issue: 3
Pages: 133-139
ISSN: 1471-0072 (ISSN-L)
1471-0080
DOI: 10.1038/nrm3522
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
Health Sciences › Medicine › Epidemiology › 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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Amino acid signalling upstream of mTOR

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