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Activation of mTORC2 by association with the ribosome

Vittoria Zinzalla1, Daniele Stracka, Wolfgang Oppliger

  • 1Biozentrum, University of Basel, CH-4056 Basel, Switzerland.

Cell
|March 8, 2011
PubMed

Insights

Ribosomes, not protein synthesis, are essential for mammalian target of rapamycin complex 2 (mTORC2) signaling. This conserved mTORC2-ribosome interaction is crucial for cell growth and cancer progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The target of rapamycin (TOR) pathway is a central regulator of cell growth and metabolism.
  • Mammalian TOR complex 2 (mTORC2) controls AGC kinases and is involved in diseases like cancer and diabetes.
  • Upstream regulators of mTORC2 activity remain incompletely understood.

Purpose of the Study:

  • To elucidate the upstream regulatory mechanisms of mTORC2 signaling.
  • To investigate the role of ribosomes and protein synthesis in mTORC2 activation.
  • To determine the physiological relevance of mTORC2 regulation in normal and cancer cells.

Main Methods:

  • Genetic screening in yeast.
  • Studies in mammalian cell lines, including melanoma and colon cancer cells.
  • Analysis of mTORC2-ribosome association and PI3K signaling.

Main Results:

  • Ribosomes, but not protein synthesis, are required for mTORC2 signaling.
  • Active mTORC2 physically associates with ribosomes.
  • Insulin-stimulated PI3K signaling enhances mTORC2-ribosome binding.
  • mTORC2-ribosome association is vital in oncogenic PI3K signaling in cancer cells.

Conclusions:

  • Ribosomes directly activate mTORC2.
  • mTORC2-ribosome interaction is a conserved mechanism for mTORC2 activation.
  • This regulatory mechanism ensures mTORC2 activity is linked to cellular growth capacity.

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