Gene interactions and pathways from curated databases and text-mining
J Immunol 2002, PMID: 12023369

A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R.

Parham, Christi; Chirica, Madaline; Timans, Jacqueline; Vaisberg, Elena; Travis, Marilyn; Cheung, Jeanne; Pflanz, Stefan; Zhang, Rebecca; Singh, Komal P; Vega, Felix; To, Wayne; Wagner, Janet; O'Farrell, Anne-Marie; McClanahan, Terrill; Zurawski, Sandra; Hannum, Charles; Gorman, Daniel; Rennick, Donna M; Kastelein, Robert A; de Waal Malefyt, Rene; Moore, Kevin W

IL-23 is a heterodimeric cytokine composed of the IL-12p40 "soluble receptor" subunit and a novel cytokine-like subunit related to IL-12p35, termed p19. Human and mouse IL-23 exhibit some activities similar to IL-12, but differ in their capacities to stimulate particular populations of memory T cells. Like IL-12, IL-23 binds to the IL-12R subunit IL-12Rbeta1. However, it does not use IL-12Rbeta2. In this study, we identify a novel member of the hemopoietin receptor family as a subunit of the receptor for IL-23, "IL-23R." IL-23R pairs with IL-12Rbeta1 to confer IL-23 responsiveness on cells expressing both subunits. Human IL-23, but not IL-12, exhibits detectable affinity for human IL-23R. Anti-IL-12Rbeta1 and anti-IL-23R Abs block IL-23 responses of an NK cell line and Ba/F3 cells expressing the two receptor chains. IL-23 activates the same Jak-stat signaling molecules as IL-12: Jak2, Tyk2, and stat1, -3, -4, and -5, but stat4 activation is substantially weaker and different DNA-binding stat complexes form in response to IL-23 compared with IL-12. IL-23R associates constitutively with Jak2 and in a ligand-dependent manner with stat3. The ability of cells to respond to IL-23 or IL-12 correlates with expression of IL-23R or IL-12Rbeta2, respectively. The human IL-23R gene is on human chromosome 1 within 150 kb of IL-12Rbeta2.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: IL23A — IL23R (direct interaction, pull down)
  • IRef Biogrid Interaction: IL23A — IL12RB1 (direct interaction, pull down)
  • IRef Biogrid Interaction: IL23R — IL12RB1 (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: IL23A — IL23R (in vitro)
  • IRef Hprd Interaction: IL23A — IL23R (in vivo)
  • IRef Hprd Interaction: IL23R — JAK2 (in vitro)
  • IRef Hprd Interaction: IL23R — JAK2 (in vivo)
  • IRef Hprd Interaction: IL12RB1 — IL23A (in vivo)
  • IRef Hprd Interaction: STAT3 — IL23R (in vivo)
  • IRef Hprd Interaction: STAT3 — IL23R (in vitro)
  • IRef Hprd Interaction: IL12RB1 — IL23R (in vivo)
  • IRef Hprd Interaction: IL12RB1 — IL23R (in vitro)
  • IRef Innatedb Interaction: IL12RB1 — IL23R (unknown, -)
  • IRef Innatedb Interaction: Complex of IL23R-IL23A-IL12B (unknown, -)
  • NCI Pathway Database IL23-mediated signaling events: STAT3 (dimer ) complex (STAT3) → STAT3 (STAT3) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: STAT3 (STAT3) → PI3K complex (PIK3CA-PIK3R1) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: STAT3 (STAT3) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: PI3K complex (PIK3CA-PIK3R1) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, activates)
    Evidence: mutant phenotype, physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: STAT1 (STAT1) → STAT1 (dimer) complex (STAT1) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT1 (STAT1) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: IL2 (IL2) → IL18/IL18R complex (IL18-IL18R1-IL18RAP) (transcription, activates)
  • NCI Pathway Database IL23-mediated signaling events: IL2 (IL2) → IFN-gamma (IFNG) (transcription, activates)
  • NCI Pathway Database IL23-mediated signaling events: IL2 (IL2) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (transcription, activates)
  • NCI Pathway Database IL23-mediated signaling events: IL18/IL18R complex (IL18-IL18R1-IL18RAP) → IFN-gamma (IFNG) (transcription, activates)
  • NCI Pathway Database IL23-mediated signaling events: IL18/IL18R complex (IL18-IL18R1-IL18RAP) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (transcription, activates)
  • NCI Pathway Database IL23-mediated signaling events: STAT4 (STAT4) → STAT3 (STAT3) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT4 (STAT4) → STAT3/STAT4 complex (STAT3-STAT4) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT4 (STAT4) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT3 (STAT3) → STAT3/STAT4 complex (STAT3-STAT4) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT3 (STAT3) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT4 (STAT4) → STAT4 (dimer) complex (STAT4) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT4 (STAT4) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: IL23 complex (IL23A-IL12B) → IL12Rbeta1/TYK2 complex (IL12RB1-TYK2) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: IL23 complex (IL23A-IL12B) → IL23R/JAK2 complex (IL23R-JAK2) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: IL23 complex (IL23A-IL12B) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: IL12Rbeta1/TYK2 complex (IL12RB1-TYK2) → IL23R/JAK2 complex (IL23R-JAK2) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: IL12Rbeta1/TYK2 complex (IL12RB1-TYK2) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: IL23R/JAK2 complex (IL23R-JAK2) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: physical interaction, other species
  • NCI Pathway Database IL23-mediated signaling events: JAK2 (JAK2) → IL23R (IL23R) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: JAK2 (JAK2) → IL23R/JAK2 complex (IL23R-JAK2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: IL23R (IL23R) → IL23R/JAK2 complex (IL23R-JAK2) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT5A (STAT5A) → STAT5A (dimer) complex (STAT5A) (modification, collaborate)
    Evidence: physical interaction
  • NCI Pathway Database IL23-mediated signaling events: STAT5A (STAT5A) → IL23/IL23R/JAK2/TYK2 complex (IL23A-IL12B-IL23R-IL12RB1-JAK2-TYK2) (modification, collaborate)
    Evidence: physical interaction
In total, 99 gene pairs are associated to this article in curated databases