TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth

Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, …, Guan KL · 2006 · Cell · Atlas ID INO2006

What this study shows

TSC2 integrates Wnt and energy signals through coordinated AMPK and GSK3 phosphorylation.

Abstract

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Mutation in the TSC2 tumor suppressor causes tuberous sclerosis complex, a disease characterized by hamartoma formation in multiple tissues. TSC2 inhibits cell growth by acting as a GTPase-activating protein toward Rheb, thereby inhibiting mTOR, a central controller of cell growth. Here, we show that Wnt activates mTOR via inhibiting GSK3 without involving beta-catenin-dependent transcription. GSK3 inhibits the mTOR pathway by phosphorylating TSC2 in a manner dependent on AMPK-priming phosphorylation.

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	Cell
Year	2006
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.cell.2006.06.055 · PMID 16959574

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 (AMPK, GSK3, TSC2)
Target	TSC2 / AMPK / GSK3 / mTOR
Model	Mammalian cells
Effect	AMPK and GSK3 coordinately phosphorylate TSC2 to integrate Wnt and energy signals controlling growth

In the Atlas

Links in the pathway map

Supports AMPK activates TSC1/TSC2
Supports mTORC1 activates Tumor growth

Cite this paper

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Inoki, K., Ouyang, H., Zhu, T., Lindvall, C., Wang, Y., Zhang, X., Yang, Q., Bennett, C., Harada, Y., Stankunas, K., Wang, C. Y., He, X., MacDougald, O. A., You, M., Williams, B. O., & Guan, K. L. (2006). TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. https://doi.org/10.1016/j.cell.2006.06.055

@article{INO2006,
  author       = {Inoki, K. and Ouyang, H. and Zhu, T. and Lindvall, C. and Wang, Y. and Zhang, X. and Yang, Q. and Bennett, C. and Harada, Y. and Stankunas, K. and Wang, C. Y. and He, X. and MacDougald, O. A. and You, M. and Williams, B. O. and Guan, K. L.},
  title        = {{TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth}},
  journal      = {Cell},
  year         = {2006},
  doi          = {10.1016/j.cell.2006.06.055},
  note         = {PMID: 16959574},
}

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 INO2006) [Data set]. https://mtor-atlas.org/study/INO2006/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_INO2006,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record INO2006},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/INO2006/},
  doi          = {10.5281/zenodo.22059963}
}

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