Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2005, PMID: 15522880

Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR).

Kusaba, Hitoshi; Ghosh, Paritosh; Derin, Rachel; Buchholz, Meredith; Sasaki, Carl; Madara, Karen; Longo, Dan L

Depending on the type of external signals, T cells can initiate multiple intracellular signaling pathways that can be broadly classified into two groups based on their sensitivity to the immunosuppressive drug cyclosporin A (CsA). Interleukin (IL)-12-mediated interferon (IFN)-gamma production by activated T cells has been shown to be CsA-insensitive. In this report, we demonstrate that the IL-12-induced CsA-resistant pathway of IFN-gamma production is sensitive to rapamycin. Rapamycin treatment resulted in the aberrant recruitment of Stat3, Stat4, and phospho-c-Jun to the genomic promoter region resulting in decreased IFN-gamma transcription. IL-12-induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the IL-12-induced interaction between mammalian target of rapamycin (mTOR) and Stat3. In accordance with this, reduction in the mTOR protein level by small interfering RNA resulted in suppression of Stat3 phosphorylation and decreased production of IFN-gamma after IL-12 stimulation. These results suggest that mTOR may play a major role in IL-12-induced IFN-gamma production by activated T cells.

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Text Mining Data

interferon-gamma → mammalian target of rapamycin (mTOR): " Interleukin-12 induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR) "

interferon (IFN)-gamma → Interleukin (IL)-12: " Interleukin (IL)-12 mediated interferon (IFN)-gamma production by activated T cells has been shown to be CsA-insensitive "

Stat3 → IL-12: " IL-12 induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the IL-12 induced interaction between mammalian target of rapamycin (mTOR) and Stat3 "

mammalian target of rapamycin (mTOR) → IL-12: " IL-12 induced phosphorylation of Stat3 on Ser-727 was affected by rapamycin, which may be due to the effect of rapamycin on the IL-12 induced interaction between mammalian target of rapamycin (mTOR) and Stat3 "

Stat3 ⊣ mTOR: " In accordance with this, reduction in the mTOR protein level by small interfering RNA resulted in suppression of Stat3 phosphorylation and decreased production of IFN-gamma after IL-12 stimulation "

IFN-gamma ⊣ mTOR: " In accordance with this, reduction in the mTOR protein level by small interfering RNA resulted in suppression of Stat3 phosphorylation and decreased production of IFN-gamma after IL-12 stimulation "

IFN-gamma → IL-12: " These results suggest that mTOR may play a major role in IL-12 induced IFN-gamma production by activated T cells "

IFN-gamma — mTOR: " These results suggest that mTOR may play a major role in IL-12 induced IFN-gamma production by activated T cells "

Manually curated Databases

  • IRef Biogrid Interaction: STAT3 — MTOR (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: STAT3 — STAT4 (in vitro)
  • IRef Hprd Interaction: STAT3 — MTOR (in vitro)
  • IRef Innatedb Interaction: IFNG — JUN (unknown, -)
  • NCI Pathway Database IL12-mediated signaling events: STAT3 (dimer ) complex (STAT3) → STAT3 (STAT3) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL12-mediated signaling events: STAT3 (STAT3) → IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL12-mediated signaling events: STAT3 (STAT3) → mTOR (MTOR) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL12-mediated signaling events: IL12/IL12R/TYK2/JAK2 complex (IL12A-IL12B-IL12RB1-IL12RB2-TYK2-JAK2) → mTOR (MTOR) (modification, activates)
    Evidence: mutant phenotype, assay, physical interaction
  • NCI Pathway Database IL12 signaling mediated by STAT4: STAT3 (dimer ) complex (STAT3) → IFN-gamma (IFNG) (transcription, activates)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL12 signaling mediated by STAT4: STAT3 (dimer ) complex (STAT3) → STAT4 (dimer) complex (STAT4) (transcription, activates)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL12 signaling mediated by STAT4: STAT3 (dimer ) complex (STAT3) → T-bet (TBX21) (transcription, activates)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL12 signaling mediated by STAT4: STAT4 (dimer) complex (STAT4) → T-bet (TBX21) (transcription, activates)
    Evidence: mutant phenotype, physical interaction, other species
In total, 34 gene pairs are associated to this article in curated databases