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 (regulatory associated protein of mTOR) and mLST8 
(mammalian lethal with SEC13 protein 8) and complex 2 (mTORC2) consisting of 
mTOR, Rictor (rapamycin-insensitive companion of mTOR), Sin1 (stress-activated 
protein kinase-interacting protein 1), mLST8 and Protor-1 or Protor-2. Both 
complexes phosphorylate the hydrophobic motifs of AGC kinase family members: 
mTORC1 phosphorylates S6K (S6 kinase), whereas mTORC2 regulates phosphorylation 
of Akt, PKCα (protein kinase Cα) and SGK1 (serum- and glucocorticoid-induced 
protein kinase 1). 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 PKCα 
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 (N-Myc downregulated gene 1) in the 
kidney. Taken together, these results suggest that Protor-1 may play a role in 
enabling mTORC2 to efficiently activate SGK1, at least in the kidney.