Gene interactions and pathways from curated databases and text-mining
Mol Cell Biol 2008, PMID: 18411301

The TSC1-TSC2 complex is required for proper activation of mTOR complex 2.

Huang, Jingxiang; Dibble, Christian C; Matsuzaki, Mika; Manning, Brendan D

The mammalian target of rapamycin (mTOR) is a protein kinase that forms two functionally distinct complexes important for nutrient and growth factor signaling. Both complexes phosphorylate a hydrophobic motif on downstream protein kinases, which contributes to the activation of these kinases. mTOR complex 1 (mTORC1) phosphorylates S6K1, while mTORC2 phosphorylates Akt. The TSC1-TSC2 complex is a critical negative regulator of mTORC1. However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown. We find that mTORC2 isolated from a variety of cells lacking a functional TSC1-TSC2 complex is impaired in its kinase activity toward Akt. Importantly, the defect in mTORC2 activity in these cells can be separated from effects on mTORC1 signaling and known feedback mechanisms affecting insulin receptor substrate-1 and phosphatidylinositol 3-kinase. Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase-activating protein activity toward Rheb. Finally, we find that the TSC1-TSC2 complex can physically associate with mTORC2 but not mTORC1. These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation.

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Text Mining Data

mTOR → TSC1-TSC2 complex: " The TSC1-TSC2 complex is required for proper activation of mTOR complex 2 "

TSC1-TSC2 complex — mTORC2: " However, how mTORC2 is regulated and whether the TSC1-TSC2 complex is involved are unknown "

mTORC2 → TSC1-TSC2 complex: " Our data also suggest that the TSC1-TSC2 complex positively regulates mTORC2 in a manner independent of its GTPase activating protein activity toward Rheb "

mTORC1 ⊣ TSC1-TSC2 complex: " These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2, which through different mechanisms promotes Akt activation "

mTORC2 → TSC1-TSC2 complex: " These data demonstrate that the TSC1-TSC2 complex inhibits mTORC1 and activates mTORC2 , which through different mechanisms promotes Akt activation "

Manually curated Databases

  • NCI Pathway Database mTOR signaling pathway: DEPTOR (DEPTOR) → mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: DEPTOR (DEPTOR) → mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5) → mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5) → TSC1/TSC2 complex (TSC1-TSC2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database mTOR signaling pathway: mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5) → AKT1 (AKT1) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
In total, 39 gene pairs are associated to this article in curated databases