Identification of protor as a novel rictor-binding component of mTOR complex-2

Laura R. Pearce, Xu Huang, Jérôme Boudeau, Rafał Pawłowski, Stephan Wullschleger, Maria Deak, Adel F. M. Ibrahim, Robert Gourlay, Mark A. Magnuson, Dario R. Alessi

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    Abstract

    The mTOR (mammalian target of rapamycin) protein kinase is an important regulator of cell growth. Two complexes of mTOR have been identified: complex 1, consisting of mTOR-Raptor (regulatory associated protein of mTOR)-mLST8 (termed mTORC1), and complex 2, comprising mTOR-Rictor (rapamycininsensitive companion of mTOR)-mLST8-Sin1 (termed mTORC2). mTORC1 phosphorylates the p70 ribosomal S6K (S6 kinase) at its hydrophobic motif (Thr389), whereas mTORC2 phosphorylates PKB (protein kinase B) at its hydrophobic motif (Ser473). In the present study, we report that widely expressed isoforms of unstudied proteins termed Protor-1 (protein observed with Rictor-1) and Protor-2 interact with Rictor and are components of mTORC2. We demonstrate that immunoprecipitation of Protor-1 or Protor-2 results in the co-immunoprecipitation of other mTORC2 subunits, but not Raptor, a specific component of mTORC1. We show that detergents such as Triton X-100 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.
    Original languageEnglish
    Pages (from-to)513-522
    Number of pages10
    JournalBiochemical Journal
    Volume405
    Issue number3
    DOIs
    Publication statusPublished - 1 Aug 2007

    Keywords

    • Carrier Proteins
    • Cell Line
    • Gene Silencing
    • Humans
    • Protein Binding
    • Protein Isoforms
    • Protein Kinases
    • TOR Serine-Threonine Kinases

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    Pearce, L. R., Huang, X., Boudeau, J., Pawłowski, R., Wullschleger, S., Deak, M., Ibrahim, A. F. M., Gourlay, R., Magnuson, M. A., & Alessi, D. R. (2007). Identification of protor as a novel rictor-binding component of mTOR complex-2. Biochemical Journal, 405(3), 513-522. https://doi.org/10.1042/BJ20070540