IL21 receptor STAT binding

Stable Identifier
R-HSA-9006873
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
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

Weinberg, K, Senadheera, S, Kaushansky, K, Habib, T

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

Veldman, G, Khan, N, Marquette, K, Wang, IM, Ling, V, Bennett, F, Luxenberg, D, Jacobs, KA, Lowe, D, Valge-Archer, VE, Carreno, BM, Collins, M

J. Immunol. 2003
12759422 IL-21 in synergy with IL-15 or IL-18 enhances IFN-gamma production in human NK and T cells

Foster, D, Matikainen, S, Strengell, M, Lehtonen, A, Sirén, J, Julkunen, I, Sareneva, T

J. Immunol. 2003
11418623 Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex

Ishii, N, Okuyama, C, Foster, D, Asao, H, Kumaki, S, Sugamura, K, Tsuchiya, S

J. Immunol. 2001
12244150 IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response

Foster, D, Matikainen, S, Strengell, M, Julkunen, I, Sareneva, T

J. Immunol. 2002
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