Sestrin2 is a leucine sensor for the mTORC1 pathway

Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, Sabatini DM · 2015 · Science · Atlas ID WOL2015

What this study shows

Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1.

Abstract

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Leucine is a proteogenic amino acid that also regulates many aspects of mammalian physiology, in large part by activating the mTOR complex 1 (mTORC1) protein kinase, a master growth controller. Amino acids signal to mTORC1 through the Rag guanosine triphosphatases (GTPases). Several factors regulate the Rags, including GATOR1, aGTPase-activating protein; GATOR2, a positive regulator of unknown function; and Sestrin2, a GATOR2-interacting protein that inhibits mTORC1 signaling.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mammalian cells) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Mammalian cells
Journal	Science
Year	2015
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.aab2674 · PMID 26449471 · Free full text (PMC4698017)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Biochemical/genetic (Sestrin2)
Target	Sestrin2 / GATOR2 / Rag / mTORC1
Model	Mammalian cells
Effect	Sestrin2 is a leucine sensor for mTORC1; leucine (not arginine) binding relieves Sestrin2 inhibition

In the Atlas

Links in the pathway map

Supports Leucine inhibits Sestrin2
Supports Sestrin2 inhibits GATOR2

Learn the biology

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Cite this paper

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Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2015). Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. https://doi.org/10.1126/science.aab2674

@article{WOL2015,
  author       = {Wolfson, R. L. and Chantranupong, L. and Saxton, R. A. and Shen, K. and Scaria, S. M. and Cantor, J. R. and Sabatini, D. M.},
  title        = {{Sestrin2 is a leucine sensor for the mTORC1 pathway}},
  journal      = {Science},
  year         = {2015},
  doi          = {10.1126/science.aab2674},
  note         = {PMID: 26449471},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record WOL2015) [Data set]. https://mtor-atlas.org/study/WOL2015/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_WOL2015,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record WOL2015},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/WOL2015/},
  doi          = {10.5281/zenodo.22059963}
}

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