Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb

Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J · 2003 · Current Biology · Atlas ID TEE2003

What this study shows

TSC1-TSC2 acts as a GTPase-activating protein (GAP) for Rheb; when TSC is inactive, Rheb accumulates in its active GTP-bound form and activates mTOR signalling.

Abstract

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Tuberous Sclerosis Complex (TSC) is a genetic disorder that occurs through the loss of heterozygosity of either TSC1 or TSC2, which encode Hamartin or Tuberin, respectively. Tuberin and Hamartin form a tumor suppressor heterodimer that inhibits the mammalian target of rapamycin (mTOR) nutrient signaling input, but how this occurs is unclear. We show that the small G protein Rheb (Ras homolog enriched in brain) is a molecular target of TSC1/TSC2 that regulates mTOR 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: Human cell lines) 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 cell lines
Journal	Current Biology
Year	2003
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/s0960-9822(03)00506-2 · PMID 12906785

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 (TSC1/TSC2)
Target	TSC1-TSC2 (Hamartin/Tuberin) / Rheb / mTOR
Model	Human cell lines
Effect	Tuberin-Hamartin (TSC1-TSC2) control mTOR by acting as a GAP complex toward Rheb

In the Atlas

Links in the pathway map

Supports TSC1/TSC2 inhibits mTORC1

Learn the biology

Want to understand the biology behind this study? → The TSC Complex — Where the Inputs Meet

Cite this paper

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Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003). Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Current Biology. https://doi.org/10.1016/s0960-9822(03)00506-2

@article{TEE2003,
  author       = {Tee, A. R. and Manning, B. D. and Roux, P. P. and Cantley, L. C. and Blenis, J.},
  title        = {{Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb}},
  journal      = {Current Biology},
  year         = {2003},
  doi          = {10.1016/s0960-9822(03)00506-2},
  note         = {PMID: 12906785},
}

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 TEE2003) [Data set]. https://mtor-atlas.org/study/TEE2003/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_TEE2003,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record TEE2003},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/TEE2003/},
  doi          = {10.5281/zenodo.22059963}
}

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