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Interleukin-21 signaling
Stable Identifier
R-HSA-9020958
DOI
10.3180/R-HSA-9020958.1
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Immune System (Homo sapiens)
Cytokine Signaling in Immune system (Homo sapiens)
Signaling by Interleukins (Homo sapiens)
Interleukin-2 family signaling (Homo sapiens)
Interleukin-21 signaling (Homo sapiens)
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Interleukin-21 (IL21) is a pleiotropic cytokine with four alpha-helical bundles. It is produced primarily by natural killer T cells, T follicular helper cells and TH17 cells, with lower levels of production by numerous other populations of lymphohaematopoietic cells (Spolski & Leonard 2014). IL21 binds Interleukin-21 receptor (IL21R, NILR) and Cytokine receptor common subunit gamma (IL2RG, GammaC).
IL21R has significant homology with the class I cytokine receptors Interleukin-2 receptor subunit beta (IL2RB) and Interleukin-4 receptor subunit alpha (IL4R) and was predicted to similarly form a complex with IL2RG. IL21R dimers can weakly bind and signal in response to IL21 but IL21 generates a much stronger response when IL21R is combined with IL2RG, which is required for a fully signaling capable IL21 receptor complex (Ozaki et al. 2000, Asao et al. 2001, Habib et al. 2002). IL21R can bind Janus kinase 1 (JAK1) (Ozaki et al. 2000) but IL2RG is required for IL21 induced signaling (Asao et al. 2001). The heteromeric IL21 receptor complex can activate JAK1, JAK3, Signal transducer and activator of transcription 1 (STAT1), STAT3, STAT4 and STAT5, depending on the cell type. In cultured T-cells IL21 induced phosphorylation of JAK1, JAK3, STAT1, STAT3 and weakly STAT5 (Asao et al. 2001). In primary CD4+ T cells IL21 induced the phosphorylation of STAT1 and STAT3 but not STAT5, whereas IL2 induced the phosphorylation of STAT5 and STAT1 but not STA3 (Bennet et al. 2003). IL21 stimulation of primary splenic B cells and the pro-B-cell line Ba-F3 induced the activation of JAK1, JAK3 and STAT5 (Habib et al. 2002). In primary human NK cells or the NK cell line NK-92, IL21 induced the activation of STAT1, STAT3, and STAT4 but not STAT5 (Strengell et al. 2002, 2003). IL21 activated STAT1 and STAT3 in human monocyte-derived macrophages (Vallières & Girard 2017).
Literature References
PubMed ID
Title
Journal
Year
24751819
Interleukin-21: a double-edged sword with therapeutic potential
Spolski, R
,
Leonard, WJ
Nat Rev Drug Discov
2014
Participants
Events
IL21 binds IL21R:JAK1
(Homo sapiens)
IL21:IL21R:JAK1 binds IL2RG:JAK3
(Homo sapiens)
IL21 receptor JAK phosphorylation
(Homo sapiens)
IL21 receptor STAT binding
(Homo sapiens)
IL21 receptor STAT phosphorylation
(Homo sapiens)
Participates
as an event of
Interleukin-2 family signaling (Homo sapiens)
Event Information
Go Biological Process
interleukin-21-mediated signaling pathway (0038114)
Orthologous Events
Interleukin-21 signaling (Bos taurus)
Interleukin-21 signaling (Canis familiaris)
Interleukin-21 signaling (Danio rerio)
Interleukin-21 signaling (Gallus gallus)
Interleukin-21 signaling (Mus musculus)
Interleukin-21 signaling (Rattus norvegicus)
Interleukin-21 signaling (Sus scrofa)
Cross References
BioModels Database
BIOMD0000000504
,
BIOMD0000000477
Authored
Jupe, S (2017-05-11)
Reviewed
Meldal, BH (2017-11-03)
Created
Jupe, S (2017-09-12)
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