PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex

Liu P, Gan W, Chin YR, Ogura K, Guo J, Zhang J, Wang B, Blenis J, Cantley LC, Toker A, Su B, Wei W · 2015 · Cancer discovery · Atlas ID LIU2015

What this study shows

PIP3 relieves SIN1 PH-domain autoinhibition to activate the mTORC2 kinase complex.

Abstract

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mTOR serves as a central regulator of cell growth and metabolism by forming two distinct complexes, mTORC1 and mTORC2. Although mechanisms of mTORC1 activation by growth factors and amino acids have been extensively studied, the upstream regulatory mechanisms leading to mTORC2 activation remain largely elusive. Here, we report that the pleckstrin homology (PH) domain of SIN1, an essential and unique component of mTORC2, interacts with the mTOR kinase domain to suppress mTOR activity.

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: Mammalian cells) 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	Mammalian cells
Journal	Cancer discovery
Year	2015
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1158/2159-8290.CD-15-0460 · PMID 26293922 · Free full text (PMC4631654)

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 (SIN1 PH domain)
Target	mTORC2 / SIN1 / PtdIns(3,4,5)P3
Model	Mammalian cells
Effect	PIP3 binds the SIN1 PH domain to relieve suppression of mTOR → activates mTORC2

In the Atlas

Links in the pathway map

Cite this paper

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Liu, P., Gan, W., Chin, Y. R., Ogura, K., Guo, J., Zhang, J., Wang, B., Blenis, J., Cantley, L. C., Toker, A., Su, B., & Wei, W. (2015). PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex. Cancer discovery. https://doi.org/10.1158/2159-8290.CD-15-0460

@article{LIU2015,
  author       = {Liu, P. and Gan, W. and Chin, Y. R. and Ogura, K. and Guo, J. and Zhang, J. and Wang, B. and Blenis, J. and Cantley, L. C. and Toker, A. and Su, B. and Wei, W.},
  title        = {{PtdIns(3,4,5)P3-Dependent Activation of the mTORC2 Kinase Complex}},
  journal      = {Cancer discovery},
  year         = {2015},
  doi          = {10.1158/2159-8290.CD-15-0460},
  note         = {PMID: 26293922},
}

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 LIU2015) [Data set]. https://mtor-atlas.org/study/LIU2015/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LIU2015,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LIU2015},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LIU2015/},
  doi          = {10.5281/zenodo.22059963}
}

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