Identification of Protor as a novel Rictor-binding component of mTOR complex-2

MRC Protein Phosphorylation Unit, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dundee DD1 5EH, Scotland, UK. ).
Biochemical Journal (Impact Factor: 4.4). 09/2007; 405(3):513-22. DOI: 10.1042/BJ20070540
Source: PubMed


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.


Available from: Adel Ibrahim
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    • "In addition to the mTOR catalytic subunit, both complexes contain: Deptor, an inhibitor of mTOR [23], mLST8 (also known as GbL) [24] [25], and the Tti1/ Tel2 complex [26], two structural proteins. Pras40, also an mTOR inhibitor, and Raptor are exclusive to mTORC1 [27] [28] [29] [30] [31] [32], whereas Rictor, mSin1 and Protor1/2 are mTORC2- specific components [28] [33] [34]. Importantly, both complexes are susceptible to such mTOR inhibitors as Rapamycin or Torin [35] [36]. "
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    Journal of Cell Death 01/2015; 1(1). DOI:10.1515/cdth-2015-0001
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    • "Raptor is essential to mTORC1 activity. The mTORC2 complex includes the rapamycin-insensitive companion of mTOR (Rictor), mammalian stress-activated MAP kinase-interacting protein 1 (mSIN1), and proteins observed with rictor 1 and 2 (PROTOR 1 and 2) (Jacinto et al., 2004, 2006; Pearce et al., 2007; Sarbassov et al., 2004) (Figure 1B). Rictor and mSIN1 are both critical to mTORC2 function. "
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    Neuron 10/2014; 84(2):275-291. DOI:10.1016/j.neuron.2014.09.034 · 15.05 Impact Factor
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    • "The mLST8 is a stable component of both mTOR complexes (Guertin et al., 2006a,b). Protor-1 interacts with Rictor, although it is not essential for the assembly of other mTORC2 subunits into the complex (Pearce et al., 2007). The Hsp70 is required for the proper formation and kinase activity of mTORC2 under basal conditions and following heat shock (Martin et al., 2008). "
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