J Immunol 2002,
PMID: 12023369
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
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IRef Biogrid Interaction:
IL23A
—
IL23R
(direct interaction, pull down)
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IRef Biogrid Interaction:
IL23A
—
IL12RB1
(direct interaction, pull down)
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IRef Biogrid Interaction:
IL23R
—
IL12RB1
(physical association, affinity chromatography technology)
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IRef Hprd Interaction:
IL23A
—
IL23R
(in vitro)
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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