Reactome | IL21 receptor STAT binding

IL21 receptor STAT binding

Stable Identifier

R-HSA-9006873

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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The IL21 receptor complex can activate 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 2016).

This is a black-box event because STAT phosphorylation is assumed to involve STAT binding though this has not been demonstrated for this receptor complex. In addition the mechanism that brings about STAT binding to the receptor, which presumably involves receptor tyrosine phosphorylation, is unclear.

Literature References

PubMed ID	Title	Journal	Year
27774606	Mechanism involved in interleukin-21-induced phagocytosis in human monocytes and macrophages Vallières, F, Girard, D	Clin. Exp. Immunol.	2017
12093291	The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3 Habib, T, Senadheera, S, Weinberg, K, Kaushansky, K	Biochemistry	2002
12517932	Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses Bennett, F, Luxenberg, D, Ling, V, Wang, IM, Marquette, K, Lowe, D, Khan, N, Veldman, G, Jacobs, KA, Valge-Archer, VE, Collins, M, Carreno, BM	J. Immunol.	2003
12759422	IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells Strengell, M, Matikainen, S, Sirén, J, Lehtonen, A, Foster, D, Julkunen, I, Sareneva, T	J. Immunol.	2003
11418623	Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex Asao, H, Okuyama, C, Kumaki, S, Ishii, N, Tsuchiya, S, Foster, D, Sugamura, K	J. Immunol.	2001
12244150	IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response Strengell, M, Sareneva, T, Foster, D, Julkunen, I, Matikainen, S	J. Immunol.	2002