A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1

Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM · 2013 · Science · Atlas ID BAR2013

What this study shows

Found the OFF switch for amino acid signaling: the GATOR1 complex is a GAP that shuts the Rag GTPases (and thus mTORC1) down when amino acids run low, while GATOR2 opposes it. GATOR1 genes are mutated in cancers, making those tumors 'blind' to starvation and hypersensitive to rapamycin.

Abstract

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The mTOR complex 1 (mTORC1) pathway promotes cell growth in response to many cues, including amino acids, which act through the Rag guanosine triphosphatases (GTPases) to promote mTORC1 translocation to the lysosomal surface, its site of activation. Although progress has been made in identifying positive regulators of the Rags, it is unknown if negative factors also exist. Here, we identify GATOR as a complex that interacts with the Rags and is composed of two subcomplexes we call GATOR1 and -2.

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: Human cells + cancer genomics) 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	Human cells + cancer genomics
Journal	Science
Year	2013
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1126/science.1232044 · PMID 23723238 · Free full text (PMC3728654)

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 (GATOR1/GATOR2)
Target	GATOR / Rag GTPases / mTORC1
Model	Human cells + cancer genomics
Effect	GATOR1 is a GAP for RagA/B (negative regulator); GATOR2 acts positively; GATOR1 lost in some cancers

In the Atlas

Links in the pathway map

Supports GATOR1 inhibits Rag GTPases
Supports GATOR2 inhibits GATOR1

Learn the biology

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Cite this paper

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Bar-Peled, L., Chantranupong, L., Cherniack, A. D., Chen, W. W., Ottina, K. A., Grabiner, B. C., Spear, E. D., Carter, S. L., Meyerson, M., & Sabatini, D. M. (2013). A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. https://doi.org/10.1126/science.1232044

@article{BAR2013,
  author       = {Bar-Peled, L. and Chantranupong, L. and Cherniack, A. D. and Chen, W. W. and Ottina, K. A. and Grabiner, B. C. and Spear, E. D. and Carter, S. L. and Meyerson, M. and Sabatini, D. M.},
  title        = {{A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1}},
  journal      = {Science},
  year         = {2013},
  doi          = {10.1126/science.1232044},
  note         = {PMID: 23723238},
}

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 BAR2013) [Data set]. https://mtor-atlas.org/study/BAR2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BAR2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BAR2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BAR2013/},
  doi          = {10.5281/zenodo.22059963}
}

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