A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation

Dalle Pezze P, Sonntag AG, Thien A, Prentzell MT, Gödel M, Fischer S, Neumann-Haefelin E, Huber TB, Baumeister R, Shanley DP, Thedieck K · 2012 · Science Signaling · Atlas ID DAL2012

What this study shows

A time-resolved, data-fitted model of the whole core insulin-mTOR network, including the mTORC1 negative feedback loop onto PI3K. Perturbing it in silico and in cells showed that TSC1-TSC2 is not a regulator of mTORC2, directly or through the feedback loop, and that mTORC2 activation runs through a PI3K variant insensitive to that loop. One of the few places where the feedback loops in the atlas are treated as a dynamical system rather than a diagram.

Abstract

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The kinase mammalian target of rapamycin (mTOR) exists in two multiprotein complexes (mTORC1 and mTORC2) and is a central regulator of growth and metabolism. Insulin activation of mTORC1, mediated by phosphoinositide 3-kinase (PI3K), Akt, and the inhibitory tuberous sclerosis complex 1/2 (TSC1-TSC2), initiates a negative feedback loop that ultimately inhibits PI3K. We present a data-driven dynamic insulin-mTOR network model that integrates the entire core network and used this model to investigate the less well understood mechanisms by which insulin regulates mTORC2.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Data-driven dynamic model of the insulin-mTOR network, tested in HeLa and other 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	Data-driven dynamic model of the insulin-mTOR network, tested in HeLa and other cell lines
Journal	Science Signaling
Year	2012
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1126/scisignal.2002469 · PMID 22457331

Extracted findings

Intervention	In silico and experimental perturbations (insulin, inhibitors, knockdowns)
Target	mTORC1; mTORC2; TSC1-TSC2; PI3K; negative feedback loop
Model	Human cell lines
Effect	mTORC2 is not regulated by TSC1-TSC2 or by the mTORC1-driven negative feedback loop

In the Atlas

Cite this paper

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Dalle Pezze, P., Sonntag, A. G., Thien, A., Prentzell, M. T., Gödel, M., Fischer, S., Neumann-Haefelin, E., Huber, T. B., Baumeister, R., Shanley, D. P., & Thedieck, K. (2012). A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation. Science Signaling. https://doi.org/10.1126/scisignal.2002469

@article{DAL2012,
  author       = {Dalle Pezze, P. and Sonntag, A. G. and Thien, A. and Prentzell, M. T. and Gödel, M. and Fischer, S. and Neumann-Haefelin, E. and Huber, T. B. and Baumeister, R. and Shanley, D. P. and Thedieck, K.},
  title        = {{A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation}},
  journal      = {Science Signaling},
  year         = {2012},
  doi          = {10.1126/scisignal.2002469},
  note         = {PMID: 22457331},
}

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 DAL2012) [Data set]. https://mtor-atlas.org/study/DAL2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_DAL2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record DAL2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/DAL2012/},
  doi          = {10.5281/zenodo.22059963}
}