Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2003, PMID: 12604610

The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.

Nojima, Hiroki; Tokunaga, Chiharu; Eguchi, Satoshi; Oshiro, Noriko; Hidayat, Sujuti; Yoshino, Ken-ichi; Hara, Kenta; Tanaka, Noriaki; Avruch, Joseph; Yonezawa, Kazuyoshi

The mammalian target of rapamycin (mTOR) controls multiple cellular functions in response to amino acids and growth factors, in part by regulating the phosphorylation of p70 S6 kinase (p70S6k) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Raptor (regulatory associated protein of mTOR) is a recently identified mTOR binding partner that also binds p70S6k and 4E-BP1 and is essential for TOR signaling in vivo. Herein we demonstrate that raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs to be required for amino acid- and mTOR-dependent regulation of these mTOR substrates in vivo. A point mutation of the TOS motif also eliminates all in vitro mTOR-catalyzed 4E-BP1 phosphorylation and abolishes the raptor-dependent component of mTOR-catalyzed p70S6k phosphorylation in vitro. Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: RPTOR — RPS6KB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RPS6KB1 — MTOR (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: EIF4EBP1 — MTOR (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: EIF4EBP1 — RPTOR (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: RPTOR — RPS6KB1 (in vitro)
  • IRef Hprd Interaction: RPS6KB1 — MTOR (in vitro)
  • IRef Hprd Interaction: RPS6KB1 — MTOR (in vivo)
  • IRef Hprd Interaction: RPTOR — EIF4EBP1 (in vitro)
  • IRef Hprd Interaction: RPTOR — EIF4EBP1 (in vivo)
  • IRef Hprd Interaction: Complex of 28 proteins (in vivo)
  • IRef Innatedb Interaction: EIF4E — EIF4EBP1 (unknown, -)
  • IRef Innatedb Interaction: EIF4EBP1 — MTOR (unknown, -)
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → 4E-BP1/eIF4E complex (EIF4EBP1-EIF4E) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → p70S6K (RPS6KB1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → eIF3/p70S6K complex (RPS6KB1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC1 complex (MTOR-MLST8-RPTOR) → p70S6K (RPS6KB1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: eIF3/p70S6K complex (RPS6KB1) → p70S6K (RPS6KB1) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
In total, 14 gene pairs are associated to this article in curated databases