Rapamycin-insensitive companion of mTOR RasGEF_N domain
SMART accession number:
SM01303
Description:
Rictor appears to serve as a scaffolding protein that is important for maintaining mTORC2 integrity. The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that forms two functionally distinct complexes, mTROC1 and mTORC2, important for nutrient and growth-factor signalling. This region is the more conserved central section that may include several individual domains. Rictor can be inhibited in the short-term by rapamycin.
Family alignment:
There are 1502 RasGEF_N_2 domains in 1502 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing RasGEF_N_2 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with RasGEF_N_2 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing RasGEF_N_2 domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and regulatesmTORC2 signaling.
Mol Cell Biol. 2010; 30: 908-21
Display abstract
The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that formstwo functionally distinct complexes important for nutrient and growth factorsignaling. While mTOR complex 1 (mTORC1) regulates mRNA translation and ribosome biogenesis, mTORC2 plays an important role in the phosphorylation and subsequent activation of Akt. Interestingly, mTORC1 negatively regulates Akt activation, butwhether mTORC1 signaling directly targets mTORC2 remains unknown. Here we showthat growth factors promote the phosphorylation of Rictor (rapamycin-insensitive companion of mTOR), an essential subunit of mTORC2. We found that Rictorphosphorylation requires mTORC1 activity and, more specifically, the p70ribosomal S6 kinase 1 (S6K1). We identified several phosphorylation sites inRictor and found that Thr1135 is directly phosphorylated by S6K1 in vitro and in vivo, in a rapamycin-sensitive manner. Phosphorylation of Rictor on Thr1135 didnot affect mTORC2 assembly, kinase activity, or cellular localization. However,cells expressing a Rictor T1135A mutant were found to have increasedmTORC2-dependent phosphorylation of Akt. In addition, phosphorylation of the Akt substrates FoxO1/3a and glycogen synthase kinase 3 alpha/beta (GSK3 alpha/beta)was found to be increased in these cells, indicating that S6K1-mediatedphosphorylation of Rictor inhibits mTORC2 and Akt signaling. Together, ourresults uncover a new regulatory link between the two mTOR complexes, wherebyRictor integrates mTORC1-dependent signaling.
Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive andraptor-independent pathway that regulates the cytoskeleton.
Curr Biol. 2004; 14: 1296-302
Display abstract
The mammalian TOR (mTOR) pathway integrates nutrient- and growth factor-derivedsignals to regulate growth, the process whereby cells accumulate mass andincrease in size. mTOR is a large protein kinase and the target of rapamycin, an immunosuppressant that also blocks vessel restenosis and has potential anticancerapplications. mTOR interacts with the raptor and GbetaL proteins to form acomplex that is the target of rapamycin. Here, we demonstrate that mTOR is alsopart of a distinct complex defined by the novel protein rictor(rapamycin-insensitive companion of mTOR). Rictor shares homology with thepreviously described pianissimo from D. discoidieum, STE20p from S. pombe, andAVO3p from S. cerevisiae. Interestingly, AVO3p is part of a rapamycin-insensitiveTOR complex that does not contain the yeast homolog of raptor and signals to the actin cytoskeleton through PKC1. Consistent with this finding, therictor-containing mTOR complex contains GbetaL but not raptor and it neitherregulates the mTOR effector S6K1 nor is it bound by FKBP12-rapamycin. We findthat the rictor-mTOR complex modulates the phosphorylation of Protein Kinase Calpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TORsignaling is conserved between yeast and mammals.
Links (links to other resources describing this domain)
