Identification of Protor as a novel Rictor-binding component of mTOR complex-2
Résumé
The mTOR protein kinase is an important regulator of cell growth. Two complexes of mTOR have been identified, complex-1, consisting of mTOR:Raptor:mLST8 (termed mTORC1) and complex-2, comprising mTOR:Rictor:mLST8:Sin1 (termed mTORC2). mTORC1 phosphorylates the p70 ribosomal S6 Kinase (S6K) at its hydrophobic motif (Thr389), whilst mTORC2 phosphorylates protein kinase B (PKB) at its hydrophobic motif (Ser473). Here we report that widely expressed isoforms of unstudied proteins termed Protor-1 (PRotein Observed with RicTOR) and Protor-2, interact with Rictor and are components of mTORC2. We demonstrate that immunoprecipitation of Protor-1 or Protor-2, result in the co-immunoprecipitation of other mTORC2 subunits, but not Raptor, a specific component of mTORC1. We show that detergents such as Triton-X100 or n-octylglucoside dissociate mTOR and mLST8 from a complex of Protor-1, Sin1 and Rictor. We also provide evidence that Rictor regulates the expression of Protor-1 and that Protor-1, is not required for the assembly of other mTORC2 subunits into a complex. Protor-1 is a novel Rictor-binding subunit of mTORC2, but further work is required to establish its role.
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