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PMID:12023369
| Citation |
Parham, C, Chirica, M, Timans, J, Vaisberg, E, Travis, M, Cheung, J, Pflanz, S, Zhang, R, Singh, KP, Vega, F, To, W, Wagner, J, O'Farrell, AM, McClanahan, T, Zurawski, S, Hannum, C, Gorman, D, Rennick, DM, Kastelein, RA, de Waal Malefyt, R and Moore, KW (2002) A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 168:5699-708 |
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| Abstract |
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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| Keywords |
Amino Acid Sequence; Animals; Dimerization; Humans; Interleukin-12/pharmacology; Interleukin-23; Interleukin-23 Subunit p19; Interleukins/metabolism; Interleukins/pharmacology; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Receptors, Cytokine/chemistry; Receptors, Cytokine/genetics; Receptors, Interleukin/chemistry; Receptors, Interleukin-12; Signal Transduction/drug effects |
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Significance
Annotations
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