Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.

By Dos D. Sarbassov, Siraj M. Ali, Do Hyung Kim, D. Guertin, R. Latek, H. Erdjument‐Bromage, Paul Tempst, David M. Sabatini. Current Biology, 2004

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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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7dc110415c5be8c1bbb2199c54a1eae13fefc59c

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Citations in the corpus

Glutaminolysis activates Rag-mTORC1 signaling. (2012, background): “…and structurally distinct complexes, termed mTORC1 and mTORC2 (Hara et al., 2002; Jacinto et al., 2004; Kim et al., 2002; Loewith et al., 2002; Sarbassov et al., 2004). mTORC1 comprises mTOR, Raptor, and mLST8 and regulates protein synthesis, ribosome biogenesis, nutrient uptake, and…”
Role of AMPK-mTOR-Ulk1/2 in the Regulation of Autophagy: Cross Talk, Shortcuts, and Feedbacks (2011, background): “mTORC2, in contrast, is unaffected by rapamycin treatment since it comprises the rapamycininsensitive companion of TOR (rictor) instead of raptor (91) (reviewed in references 94 and 110).”
Active-Site Inhibitors of mTOR Target Rapamycin-Resistant Outputs of mTORC1 and mTORC2 (2009, background): “Previous analysis of mTORC2 function using RNAi revealed a role for mTORC2 in the control of the actin cytoskeleton [3,4], yet these findings were not confirmed in primary MEFs lacking mTORC2 [15,17].”
The PTEN–PI3K pathway: of feedbacks and cross-talks (2008, background): “Recently, mTOR was found to interact with a different subset of proteins in a complex called as mTORC2 (Sarbassov et al., 2004, 2005).”
TOR signaling in growth and metabolism. (2006, methodology): “mTORC2 also signals to the actin cytoskeleton (Jacinto et al., 2004; Sarbassov et al., 2004).”
The mTOR Signalling Pathway in Human Cancer (2012, background): “Upon activation, Rho1 interacts and activates PKC1, which in turn signals to the actin cytoskeleton via MAPK pathway [97,98]. mTORC2 also signals to the actin cytoskeleton, and although the direct targets of mTORC2 are unknown, this signalling may involve PKCα and the small GTPases Rho and Rac [12,3”