Reactome | Interleukin-27 binds Interleukin-27 receptor

Interleukin-27 binds Interleukin-27 receptor

Stable Identifier

R-HSA-448427

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane, cytosol

Synonyms

IL27(complex of IL27:EBI3) binds IL27R(complex of IL27RA:IL6ST), IL27:EBI3 binds IL27RA:IL6ST

ReviewStatus

5/5

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Interleukin-27 binds Interleukin-27 receptor

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A naturally occurring soluble form of Interleukin-27 receptor subunit, alpha(IL-27Ralpha) is termed soluble Interleukin-27 receptor subunit alpha (sIL-27Ralpha)and it is produced by human activated CD4(+) and CD8(+) T cells, B cells, myeloid cells, and various cell lines. Importantly, natural sIL-27Ralpha binds rIL-27(the heterodimer composed of the Interleukin-27 subunit alpha and Interleukin-27 subunit beta), inhibits IL-27 binding to its cell surface receptor and is a potent inhibitor of IL-27 signaling, as shown by its ability to specifically block IL-27-mediated STAT activation, at low molar excess over IL-27. Interleukin-27 is a heterodimer composed of Interleukin-27 subunit alpha (IL27) and Epstein-Barr virus-induced gene 3 (EBI3). It binds to the Interleukin-27 heterodimeric receptor, which is composed of Interleukin-27 receptor subunit alpha (IL27RA, WSX-1) and Interleukin-6 receptor subunit beta (IL6ST, gp130). IL6ST is a signal transducing protein that is a component of several other cytokine receptors including the Interleukin-6 and Interleukin-11 receptors (Pflanz et al. 2004). In the absence of IL27RA, Interleukin-27 can bind to IL6ST but with low affinity (Jia et al. 2016).
Regulation: IL27RA can be cleaved releasing a soluble form (sIL27RA) that can bind to Interleukin-27 and antagonize Interleukin-27 binding to its heterodimer receptor (Dietrich et al. 2014).

Literature References

PubMed ID	Title	Journal	Year
27119567	IL-27 Promotes Proliferation of Human Leukemic Cell Lines Through the MAPK/ERK Signaling Pathway and Suppresses Sensitivity to Chemotherapeutic Drugs Wadhwa, M, Dilger, P, Bird, C, Jia, H	J. Interferon Cytokine Res.	2016
14764690	WSX-1 and glycoprotein 130 constitute a signal-transducing receptor for IL-27 Kastelein, RA, Phillips, JH, Vaisberg, E, Rosales, R, Hibbert, L, Pflanz, S, Bazan, JF, Mattson, J, de Waal Malefyt, R, McClanahan, TK	J Immunol	2004
24771852	A soluble form of IL-27Rα is a natural IL-27 antagonist Devergne, O, Dietrich, C, Candon, S, Ruemmele, FM	J. Immunol.	2014