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Differential regulation of mTORC1 by leucine and glutamine
Open accessAbstract
Getting specific about amino acid sensing: The protein kinase complex mTORC1 regulates growth and metabolism, and its activity is controlled in response to the abundance of cellular amino acids. Jewell et al. report that control of mTORC1 in response to glutamine does not require the Rag guanosine triphosphatase (GTPase) implicated in the sensing of other amino acids such as leucine (see the Perspective by Abraham). For sensing of glutamine, another GTPase, Arf1, was required. Distinct mechanisms thus appear to couple various amino acids to signaling by the mTORC1 complex. Science , this issue p. 194 ; see also p. 128
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“Evidence has shown that glutamine activates the mTORC1 pathway via Arf1 rather than via the Rag GTPase complex in MEFs190.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [190]
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Metadata
- Authors
- Jewell, J. L., Kim, Y. C., Russell, R. C., Yu, F.-X., Park, H. W., Plouffe, S. W., Tagliabracci, V. S., & Guan, K.-L.
- Affiliations
- University of California San Diego (US)
- Fudan University (CN)
- Corresponding author
- Kim, Young Chul
- Russell, Ryan C.
- Guan, Kun-Liang
- ORCID
- Venue
- Science
- Published
- 2015-01-09
- Volume
- 347
- Issue
- 6218
- Pages
- 194-198
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4384888
- OpenAlex
- W2157760261
- Cited by
- 757
- References
- 35
- Citations by year
- 2026: 37 · 2025: 45 · 2024: 58 · 2023: 62 · 2022: 75 · 2021: 102 · 2020: 81 · 2019: 54 · 2018: 60 · 2017: 57 · 2016: 65 · 2015: 60
- FWCI
- 35.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc)
- PubMed Central (acceptedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (R01GM051586, R01CA108941, T32CA121938, T32GM007752, K99DK099254)
- Department of Defense (W81XWH-13-1-055)
- The Hartwell Foundation
- Canadian Institutes of Health Research
- 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
- mTORC1, leucine, glutamine, Rag GTPases, Ragulator complex, V-ATPase, lysosomal translocation, Arf1, amino acid signaling, cell growth regulation, raga
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Regulatory-Associated Protein of mTOR, Animals, Enzyme Activation, Glutamine, Humans, Leucine, Lysosomes, Mice, Knockout, Monomeric GTP-Binding Proteins, ADP-Ribosylation Factor 1, Protein Transport, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Mice, Gene Knockdown Techniques, HEK293 Cells, TOR Serine-Threonine Kinases
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