Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1

Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM · 2006 · Developmental Cell · Atlas ID GUE2006

What this study shows

The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice.

Abstract

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The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficient for raptor, rictor, or mLST8. Like mice null for mTOR, those lacking raptor die early in development. However, mLST8 null embryos survive until e10.5 and resemble embryos missing rictor.

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: Knockout mice (raptor/rictor/mLST8)) 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	Knockout mice (raptor/rictor/mLST8)
Journal	Developmental Cell
Year	2006
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1016/j.devcel.2006.10.007 · PMID 17141160

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	Genetic (raptor / rictor / mLST8 knockout mice)
Target	mTORC1 vs mTORC2 / Akt-FOXO / PKCα
Model	Knockout mice
Effect	mTORC2 (rictor/mLST8) is required for Akt-FOXO and PKCα signaling but not S6K1; raptor/mTOR-null mice die early

In the Atlas

Links in the pathway map

Supports mLST8 required-for mTORC2
Supports Akt/PKB inhibits FOXO1/3

Learn the biology

Want to understand the biology behind this study? → What is mTOR?

Cite this paper

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Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., & Sabatini, D. M. (2006). Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Developmental Cell. https://doi.org/10.1016/j.devcel.2006.10.007

@article{GUE2006,
  author       = {Guertin, D. A. and Stevens, D. M. and Thoreen, C. C. and Burds, A. A. and Kalaany, N. Y. and Moffat, J. and Brown, M. and Fitzgerald, K. J. and Sabatini, D. M.},
  title        = {{Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1}},
  journal      = {Developmental Cell},
  year         = {2006},
  doi          = {10.1016/j.devcel.2006.10.007},
  note         = {PMID: 17141160},
}

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 GUE2006) [Data set]. https://mtor-atlas.org/study/GUE2006/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GUE2006,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GUE2006},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GUE2006/},
  doi          = {10.5281/zenodo.22059963}
}

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