Cited by 765PI3K/AKT/mTOR signaling in cancerAutophagy in Disease and TherapyMetabolism, Diabetes, and Cancer

Differential regulation of mTORC1 by leucine and glutamine

Open access
Jewell, Jenna L., Kim, Young Chul, Russell, Ryan C., Yu, Fa-Xing, Park, Hyun Woo, Plouffe, Steven W., Tagliabracci, Vincent S., Guan, Kun-Liang·2015·Science

Abstract

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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  • Glutamine activates the mTORC1 pathway via Arf1 rather than via the Rag GTPase complex in MEFs.

    “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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  1. [9]Bar-Peled L Science 340 1100 1106 2013 23723238 PMC3728654
  2. [13]Bar-Peled L Schweitzer LD Zoncu R Sabatini DM Cell 150 1196 1208 2012 22980980 PMC3517996
  3. [23]D’Souza-Schorey C Chavrier P Nat Rev Mol Cell Biol 7 347 358 2006 16633337

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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
Venue
Science
Published
2015-01-09
Volume
347
Issue
6218
Pages
194-198
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
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 · 2014: 1
FWCI
35.04
Type
journal article
Language
en
Open access
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
  • Health Sciences › Medicine › Epidemiology › 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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