Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton

AbstractThe 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

Isolation and characterization of yeast mutants in glycosyl phosphatidylinositol membrane anchoring of protein

Thesis (B.S.) in Biochemistry--University of Illinois at Urbana-Champaign, 1994.Includes bibliographical references (leaves 30-31)U of I OnlyTheses restricted to UIUC community onl