DOC_WD40_RPTOR_TOS_1

The mammalian target of rapamycin mTOR, also known as FRAP, is a member of the PIK-related superfamily of protein serine/theronine kinases that was first identified in Saccharomyces cerevisiae (Oshiro,2007). The TOR pathway is an emerging target for the treatment of cancer, diabetes and obesity. TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many of them are phosphorylated indirectly. TOR participates in at least two distinct multiprotein complexes TORC1 and TORC2. These complexes play important role in the regulation of cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription (Beugnet,2003). Two short motifs have been reported in the targets of TOR, the TOS motif (TOR signalling motif) and the RAIP motif. However, the RAIP motif is not characterised well enough to be included in ELM.
In mammals mTOR, (mammalian TOR), regulates protein synthesis through the phosphorylation and inactivation of the repressor of mRNA translation, eukaryotic initiation factor 4E-binding protein (4E-BP1), and through the phosphorylation and activation of S6 kinase (S6K1). mTOR exists in two distinct complexes within cells: one (mTORC1) that contains mTOR, mLst8 and raptor and another (mTORC2) containing mTOR, mLst8, mSin1 and rictor (Schalm,2002). In order to phosphorylate its substrates in the TORC1 complex, mTOR needs an adaptor protein (raptor) that binds to S6K1 and 4E-BP1 (16824195). The interaction of raptor with S6K1 and 4E-BP1 is mediated by the TOS motif that is present in the N-terminus of S6-beta kinases and C-terminus of 4E-BP1. The TOS motif is currently only known from metazoan organisms. However, the TORC1 complex and highly conserved raptor orthologues are present in both Saccharomyces cerevisiae (Kog1) and Schizosaccharomyces pombe (Mip1). It is possible that the TOS motif exists in other Eukaryotic lineages but diverges from the metazoan motif pattern and so needs rediscovery.