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Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney

Laura R Pearce1, Eeva M Sommer, Kei Sakamoto

  • 1MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

The Biochemical Journal
|March 19, 2011
PubMed

Insights

Protor-1, a component of mTORC2, is crucial for activating SGK1 kinase and its substrate NDRG1 in the kidney. Loss of Protor-1 impairs this activation, suggesting a specific role in mTORC2 signaling.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • Biochemistry

Background:

  • Mammalian target of rapamycin (mTOR) is vital for cell growth and a cancer therapeutic target.
  • mTOR functions in two complexes: mTORC1 and mTORC2.
  • mTORC2 phosphorylates AGC kinase family members, including Akt, PKCα, and SGK1.

Purpose of the Study:

  • To investigate the function of Protor isoforms (Protor-1 and Protor-2) in mTORC2 signaling.
  • To determine the impact of Protor deficiency on mTORC2 substrate phosphorylation.

Main Methods:

  • Generation of single and double Protor-1 and Protor-2 knockout mice.
  • Analysis of mTORC2 component expression and complex assembly.
  • Assessment of mTORC2 substrate phosphorylation (Akt, PKCα, SGK1, NDRG1).

Main Results:

  • Protor knockout did not affect mTORC2 component expression or complex formation.
  • Protor deficiency did not alter Akt or PKCα phosphorylation.
  • Protor-1 knockout mice showed reduced SGK1 and NDRG1 phosphorylation in the kidney.

Conclusions:

  • Protor-1 appears essential for efficient mTORC2-mediated activation of SGK1 and NDRG1, particularly in renal tissue.
  • Protor-2 does not seem to compensate for Protor-1 loss in SGK1 activation.
  • These findings highlight a specific role for Protor-1 in regulating SGK1 signaling within mTORC2.

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