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Updated: Mar 8, 2026

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
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Published on: May 17, 2014

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Localization of mTORC2 activity inside cells

Michael Ebner1,2, Benjamin Sinkovics2,3, Magdalena Szczygieł4

  • 1Max F. Perutz Laboratories, Department of Structural and Computational Biology, Vienna BioCenter, 1030 Vienna, Austria.

The Journal of Cell Biology
|February 2, 2017
PubMed

Insights

Growth factors regulate cell growth by influencing mammalian target of rapamycin (mTOR) complex 2 (mTORC2) activity. This study reveals mTORC2

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mammalian target of rapamycin (mTOR) complex 2 (mTORC2) phosphorylates protein kinase Akt, linking extracellular signals to cell growth and proliferation.
  • The precise mechanisms by which growth factors regulate mTORC2 activity towards Akt remain largely uncharacterized.

Purpose of the Study:

  • To investigate the intracellular localization and regulation of mTORC2 activity by growth factors.
  • To develop a reporter system for monitoring endogenous mTORC2 activity and localization.

Main Methods:

  • Utilized advanced imaging techniques and biochemical assays.
  • Examined the localization of mSin1, an essential component of mTORC2.
  • Developed a novel reporter for intracellular mTORC2 activity.

Main Results:

  • Demonstrated that mTORC2 activity is localized to the plasma membrane, mitochondria, and endosomal vesicles within cells.
  • Showed that plasma membrane-localized mTORC2, via the Sin1 pleckstrin homology domain, is independent of phosphoinositide 3-kinase (PI3K) and growth factors.
  • Confirmed that recruitment to the membrane is sufficient for growth factor-induced Akt phosphorylation.

Conclusions:

  • Identified spatially distinct mTORC2 populations with differential sensitivity to PI3K within cells.
  • Suggests that intracellular localization plays a crucial role in regulating mTORC2 activity towards Akt.

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