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

Laura R Pearce , Eeva M Sommer , Kei Sakamoto , Stephan Wullschleger , Dario R Alessi (1)

1 MRC Protein Phosphorylation Unit, Department of Biochemistry

The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth and is a key target for therapeutic intervention in cancer. Two complexes of mTOR have been identified: complex 1 (mTORC1), consisting of mTOR, Raptor and mLST8 and complex 2 (mTORC2) consisting of mTOR, Rictor, Sin1, mLST8 and Protor-1 or Protor-2. Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members: mTORC1 phosphorylates S6K, while mTORC2 regulates phosphorylation of Akt, PKC and SGK1. To investigate the roles of the Protor isoforms, we generated single as well as double Protor-1 and Protor-2 knockout mice and studied how activation of known mTORC2 substrates was affected. We observed that loss of Protor-1 and/or Protor-2 did not affect the expression of the other mTORC2 components, nor their ability to assemble into an active complex. Moreover, Protor knockout mice display no defects in the phosphorylation of Akt and PKC at their hydrophobic or turn motifs. Strikingly, we observed that Protor-1 knockout mice displayed markedly reduced hydrophobic motif phosphorylation of SGK1 and its physiological substrate NDRG1 in the kidney. These data suggest that Protor-1 may play a role in enabling mTORC2 to efficiently activate SGK1, at least in the kidney.

Mots clés: Life Sciences

Laura R Pearce, Eeva M Sommer, Kei Sakamoto, Stephan Wullschleger, Dario R Alessi. Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney. Biochemical Journal, 2011, 436 (1), pp.169-179. ⟨10.1042/BJ20102103⟩. ⟨hal-00591708⟩