Gene interactions and pathways from curated databases and text-mining
Curr Biol 2004, PMID: 15268862

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

Sarbassov, D D; Ali, Siraj M; Kim, Do-Hyung; Guertin, David A; Latek, Robert R; Erdjument-Bromage, Hediye; Tempst, Paul; Sabatini, David M

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.

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Text Mining Data

S6K1 → mTOR: " 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 "

S6K1 — FKBP12-rapamycin: " 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 "

raptor — FKBP12-rapamycin: " 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 "

mTOR — FKBP12-rapamycin: " 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 "

Manually curated Databases

  • IRef Biogrid Interaction: RICTOR — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPTOR — FKBP1A (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FKBP1A — MTOR (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPTOR — MTOR (physical association, affinity chromatography technology)
  • MIPS CORUM mTOR-RICTOR complex: mTOR-RICTOR complex complex (MTOR-MLST8-RICTOR)
  • MIPS CORUM mTOR-RAPTOR complex: mTOR-RAPTOR complex complex (MTOR-MLST8-RPTOR)
  • IRef Corum Interaction: Complex of MLST8-RICTOR-MTOR-MTOR-RICTOR-MLST8 (association, anti bait coimmunoprecipitation)
  • Gene Ontology Complexes TORC2 complex: TORC2 complex complex (PINK1-RICTOR-TTI1-RPL23A)
  • IRef Hprd Interaction: Complex of MTOR-GNB1L-RICTOR-RICTOR-GNB1L-MTOR-GNB1L-MTOR-RICTOR (in vivo)
  • NCI Pathway Database mTOR signaling pathway: RAC1/GTP complex (RAC1) → mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) (regulation of actin cytoskeleton organization, collaborate)
    Evidence: mutant phenotype
  • NCI Pathway Database mTOR signaling pathway: RAC1/GTP complex (RAC1) → Paxillin (PXN) (regulation of actin cytoskeleton organization, collaborate)
    Evidence: mutant phenotype
  • NCI Pathway Database mTOR signaling pathway: RAC1/GTP complex (RAC1) → RHOA/GTP complex (RHOA) (regulation of actin cytoskeleton organization, collaborate)
    Evidence: mutant phenotype
  • NCI Pathway Database mTOR signaling pathway: mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) → Paxillin (PXN) (regulation of actin cytoskeleton organization, activates)
    Evidence: mutant phenotype
  • NCI Pathway Database mTOR signaling pathway: mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) → RHOA/GTP complex (RHOA) (regulation of actin cytoskeleton organization, activates)
    Evidence: mutant phenotype
  • NCI Pathway Database mTOR signaling pathway: Paxillin (PXN) → RHOA/GTP complex (RHOA) (regulation of actin cytoskeleton organization, collaborate)
    Evidence: mutant phenotype
  • NCI Pathway Database mTOR signaling pathway: mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) → PKC alpha (PRKCA) (modification, activates)
    Evidence: mutant phenotype
In total, 45 gene pairs are associated to this article in curated databases