| Abstract: |
The mammalian TOR (mTOR) pathway integrates nutrient- and growth factor-derived signals to regulate growth, the process whereby cells accumulate mass and increase in size. mTOR is a large protein kinase and the target of rapamycin, an immunosuppressant that also blocks vessel restenosis and has potential anticancer applications. mTOR interacts with the raptor and GβL proteins [1-3] to form a complex that is the target of rapamycin. Here, we demonstrate that mTOR is also part of a distinct complex defined by the novel protein rictor (rapamycin-insensitive companion of mTOR). Rictor shares homology with the previously described pianissimo from D. discoidieum [4], STE20p from S. pombe [5], and AVO3p from S. cerevisiae [6, 7]. Interestingly, AVO3p is part of a rapamycin-insensitive TOR complex that does not contain the yeast homolog of raptor and signals to the actin cytoskeleton through PKC1 [6]. Consistent with this finding, the rictor-containing mTOR complex contains GβL but not raptor and it neither regulates the mTOR effector S6K1 nor is it bound by FKBP12-rapamycin. We find that the rictor-mTOR complex modulates the phosphorylation of Protein Kinase C α (PKCα) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals. |
| Keywords: |
carrier protein; genetics; comparative study; molecular genetics; proteins; animal; metabolism; mammalia; animals; actin; protein kinases; protein; small interfering rna; rna, small interfering; drosophila; rna interference; hela cell; hela cells; transfection; phosphorylation; animalia; fluorescent antibody technique; amino acid sequence; conserved sequence; molecular sequence data; genetic transfection; sequence alignment; nucleotide sequence; mammalian target of rapamycin; carrier proteins; immunoblotting; dna sequence; protein kinase c; serodiagnosis; dna primers; primer dna; actins; cytoskeleton; protein kinase; rapamycin; sirolimus; gene structure; polyacrylamide gel electrophoresis; electrophoresis, polyacrylamide gel; protein kinase c alpha; sequence analysis, dna; protein kinase c-alpha; raptores; precipitin tests; humans; human; article; raptor protein, human; rictor protein, human; gene components
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