The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C

Facchinetti V, Ouyang W, Wei H, Soto N, Lazorchak A, Gould C, Lowry C, Newton AC, Mao Y, Miao RQ, Sessa WC, …, Jacinto E · 2008 · EMBO Journal · Atlas ID FAC2008

What this study shows

Cells lacking the mTORC2 components mTOR, SIN1 or rictor lost phosphorylation of Akt and of conventional protein kinase C at the turn motif, a site near the end of the kinase domain. This phosphorylation did not depend on growth factors, and the authors reported the same function in yeast. Turn-motif phosphorylation helped newly made Akt and PKC fold correctly and stay stable; without it, Akt was held by the chaperone Hsp90 and protected from ubiquitin-mediated breakdown. mTORC2 controlled the Akt turn-motif and hydrophobic-motif (Ser473) sites independently in vivo and phosphorylated both directly in vitro. Boundary: Cell culture, yeast and in vitro kinase assays, with mouse tissue for the in vivo site analysis. Shows a protein-maturation role of mTORC2, not an organismal phenotype. Drafted from the abstract only.

Abstract

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The target of rapamycin (TOR), as part of the rapamycin-sensitive TOR complex 1 (TORC1), regulates various aspects of protein synthesis. Whether TOR functions in this process as part of TORC2 remains to be elucidated. Here, we demonstrate that mTOR, SIN1 and rictor, components of mammalian (m)TORC2, are required for phosphorylation of Akt and conventional protein kinase C (PKC) at the turn motif (TM) site. This TORC2 function is growth factor independent and conserved from yeast to mammals.

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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: Mouse embryonic fibroblasts lacking mTORC2 components (SIN1, rictor, mTOR) and human cell lines; yeast; mouse tissue; 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	Mouse embryonic fibroblasts lacking mTORC2 components (SIN1, rictor, mTOR) and human cell lines; yeast; mouse tissue; in vitro kinase assays
Journal	EMBO Journal
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/emboj.2008.120 · PMID 18566586 · Free full text (PMC2486276)

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 loss of mTOR, SIN1 or rictor (mTORC2 disruption)
Target	Akt and conventional PKC turn-motif phosphorylation, folding and stability
Model	Mouse cells, human cells, yeast
Effect	Loss of mTORC2 abolishes Akt/PKC turn-motif phosphorylation and destabilises newly synthesised Akt and PKC

In the Atlas

Links in the pathway map

Supports mTORC2 activates Akt/PKB

Cite this paper

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Facchinetti, V., Ouyang, W., Wei, H., Soto, N., Lazorchak, A., Gould, C., Lowry, C., Newton, A. C., Mao, Y., Miao, R. Q., Sessa, W. C., Qin, J., Zhang, P., Su, B., & Jacinto, E. (2008). The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO Journal. https://doi.org/10.1038/emboj.2008.120

@article{FAC2008,
  author       = {Facchinetti, V. and Ouyang, W. and Wei, H. and Soto, N. and Lazorchak, A. and Gould, C. and Lowry, C. and Newton, A. C. and Mao, Y. and Miao, R. Q. and Sessa, W. C. and Qin, J. and Zhang, P. and Su, B. and Jacinto, E.},
  title        = {{The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C}},
  journal      = {EMBO Journal},
  year         = {2008},
  doi          = {10.1038/emboj.2008.120},
  note         = {PMID: 18566586},
}

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 FAC2008) [Data set]. https://mtor-atlas.org/study/FAC2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_FAC2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record FAC2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/FAC2008/},
  doi          = {10.5281/zenodo.22059963}
}

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