Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner
Open accessAbstract
Amino acids exert modulatory effects on proteins involved in control of mRNA translation in animal cells through the target of rapamycin (TOR) signaling pathway. Here we use oocytes of Xenopus laevis to investigate mechanisms by which amino acids are "sensed" in animal cells. Small ( approximately 48%) but physiologically relevant increases in intracellular but not extracellular total amino acid concentration (or Leu or Trp but not Ala, Glu, or Gln alone) resulted in increased phosphorylation of p70(S6K) and its substrate ribosomal protein S6. This response was inhibited by rapamycin, demonstrating that the effects require the TOR pathway. Alcohols of active amino acids substituted for amino acids with lower efficiency. Oocytes were refractory to changes in external amino acid concentration unless surface permeability of the cell to amino acids was increased by overexpression of the System L amino acid transporter. Amino acid-induced, rapamycin-sensitive activation of p70(S6K) was conferred when System L-expressing oocytes were incubated in extracellular amino acids, supporting intracellular localization of the putative amino acid sensor. In contrast to lower eukaryotes such as yeast, which possess an extracellular amino acid sensor, our findings provide the first direct evidence for an intracellular location for the putative amino acid sensor in animal cells that signals increased amino acid availability to TOR/p70(S6K).
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The amino acid sensing system is incredibly sensitive, with an approximately 7% increase in intracellular leucine leading to 50% maximal activation of mTORC1.
“Cell based work has shown that this amino acid sensing system is incredibly sensitive with an ~7% increase in intracellular leucine leading to 50% maximal activation of mTORC1 [97].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [97]
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Self-citation
- Authors
- Christie, G. R., Hajduch, E., Hundal, H. S., Proud, C. G., & Taylor, P. M.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Proud, Christopher G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 277
- Issue
- 12
- Pages
- 9952-9957
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1988070091
- Cited by
- 125
- References
- 38
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 3 · 2014: 7 · 2013: 7 · 2012: 8
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- amino acid sensing, p70 S6 kinase, target of rapamycin, TOR signaling, S6 phosphorylation, system L amino acid transporter, mRNA translation regulation, Xenopus oocytes, rapamycin, amino acid availability
- MeSH terms
- Alanine, Alcohols, Amino Acids, Animals, Dose-Response Relationship, Drug, Glutamine, Leucine, Oocytes, Phosphorylation, Protein Binding, Time Factors, Tryptophan, Xenopus laevis, Blotting, Western, Signal Transduction, Glutamic Acid, Ribosomal Protein S6 Kinases, Sirolimus, Amino Acid Motifs
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