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 GbetaL proteins 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, STE20p from S. pombe, and AVO3p from S. cerevisiae. 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. Consistent with this finding, the rictor-containing mTOR complex contains GbetaL 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 alpha (PKCalpha) and the actin cytoskeleton, suggesting that this aspect of TOR signaling is conserved between yeast and mammals.
Pubmed ID: 15268862 RIS Download
Mesh terms: Actins | Adaptor Proteins, Signal Transducing | Amino Acid Sequence | Animals | Carrier Proteins | Conserved Sequence | Cytoskeleton | DNA Primers | Drosophila | Electrophoresis, Polyacrylamide Gel | Fluorescent Antibody Technique | Gene Components | HeLa Cells | Humans | Immunoblotting | Molecular Sequence Data | Phosphorylation | Precipitin Tests | Protein Kinase C | Protein Kinase C-alpha | Protein Kinases | Proteins | RNA Interference | RNA, Small Interfering | Sequence Alignment | Sequence Analysis, DNA | Sirolimus | TOR Serine-Threonine Kinases | Transfection
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