TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling

Inoki K, Li Y, Zhu T, Wu J, Guan KL · 2002 · Nature Cell Biology · Atlas ID INO2002

What this study shows

Akt directly phosphorylates and inactivates TSC2, disrupting the TSC1-TSC2 complex and releasing its inhibition of mTOR - the link between growth-factor/insulin signaling and mTORC1 activation.

Abstract

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Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by the formation of hamartomas in a wide range of human tissues. Mutation in either the TSC1 or TSC2 tumour suppressor gene is responsible for both the familial and sporadic forms of this disease. TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation).

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	Nature Cell Biology
Year	2002
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ncb839 · PMID 12172553

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 (Akt phosphorylation of TSC2)
Target	TSC2 / Akt / mTOR
Model	Human cell lines
Effect	Akt phosphorylates and inactivates TSC2 → relieves mTOR inhibition (links insulin/growth factors to mTORC1)

In the Atlas

Links in the pathway map

Supports Akt/PKB inhibits TSC1/TSC2

Learn the biology

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Cite this paper

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Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K. L. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nature Cell Biology. https://doi.org/10.1038/ncb839

@article{INO2002,
  author       = {Inoki, K. and Li, Y. and Zhu, T. and Wu, J. and Guan, K. L.},
  title        = {{TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling}},
  journal      = {Nature Cell Biology},
  year         = {2002},
  doi          = {10.1038/ncb839},
  note         = {PMID: 12172553},
}

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 INO2002) [Data set]. https://mtor-atlas.org/study/INO2002/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_INO2002,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record INO2002},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/INO2002/},
  doi          = {10.5281/zenodo.22059963}
}

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