Akt regulates growth by directly phosphorylating Tsc2

Potter CJ, Pedraza LG, Xu T · 2002 · Nature Cell Biology · Atlas ID POT2002

What this study shows

Working in fruit flies, the authors showed that Akt directly phosphorylates the Drosophila Tsc2 protein in vitro at two conserved residues, Ser924 and Thr1518. Tsc2 with these sites mutated no longer responded to Akt signalling, and its complex with Tsc1 became more stable. Turning up Akt signalling in fly tissue increased cell size, broke up the Tsc1-Tsc2 complex and changed where the two proteins sat in the cell. Expressing a Tsc2 mutant that Akt cannot phosphorylate blocked the growth signals from Akt, which led the authors to propose Tsc2 as the key Akt target for growth in the insulin pathway. Boundary: Drosophila tissues and in vitro biochemistry with overexpressed mutant proteins; the claim that Tsc2 carries all Akt growth signals was tested in flies, not in mammals.

Abstract

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The direct mechanism by which the serine/threonine kinase Akt (also known as protein kinase B (PKB)) regulates cell growth is unknown. Here, we report that Drosophila melanogaster Akt/PKB stimulates growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex. We show that Akt/PKB directly phosphorylates Drosophila Tsc2 in vitro at the conserved residues, Ser 924 and Thr 1518. Mutation of these sites renders Tsc2 insensitive to Akt/PKB signalling, increasing the stability of the Tsc1-Tsc2 complex within the cell.

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: Drosophila melanogaster genetics (eye/tissue growth, Akt overexpression, Tsc2 site mutants); in vitro kinase assays) 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	Drosophila melanogaster genetics (eye/tissue growth, Akt overexpression, Tsc2 site mutants); in vitro kinase assays
Journal	Nature Cell Biology
Year	2002
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ncb840 · PMID 12172554

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	Akt/PKB overexpression; Tsc2 S924/T1518 phospho-site mutants
Target	Tsc2 phosphorylation; Tsc1-Tsc2 complex; cell size
Model	Drosophila melanogaster
Effect	Akt phosphorylates Tsc2 and disrupts the Tsc1-Tsc2 complex -> increased cell growth

In the Atlas

Links in the pathway map

Supports Akt/PKB inhibits TSC1/TSC2

Cite this paper

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Potter, C. J., Pedraza, L. G., & Xu, T. (2002). Akt regulates growth by directly phosphorylating Tsc2. Nature Cell Biology. https://doi.org/10.1038/ncb840

@article{POT2002,
  author       = {Potter, C. J. and Pedraza, L. G. and Xu, T.},
  title        = {{Akt regulates growth by directly phosphorylating Tsc2}},
  journal      = {Nature Cell Biology},
  year         = {2002},
  doi          = {10.1038/ncb840},
  note         = {PMID: 12172554},
}

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 POT2002) [Data set]. https://mtor-atlas.org/study/POT2002/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_POT2002,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record POT2002},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/POT2002/},
  doi          = {10.5281/zenodo.22059963}
}

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