Reactome | JAK3 in IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3 is phosphorylated

JAK3 in IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3 is phosphorylated

Stable Identifier

R-HSA-8983063

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

plasma membrane, cytosol, extracellular region

Synonyms

JAK3 is phosphorylated after IL7:IL7R binding

ReviewStatus

5/5

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JAK3 in IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3 is phosphorylated

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Interleukin-7 (IL7) signaling is believed to resemble that of other gammaC family receptors, based on detailed studies of the Interleukin-2 receptor. Extending this model to IL7 suggested a series of events that bring Tyrosine-protein kinase JAK1 (JAK1) and Tyrosine-protein kinase JAK3 (JAK3) into proximity within the complex IL7:IL7R:JAK1:IL2RG:JAK3. Cytoplasmic domains of the receptor chains re-orient so that their associated kinases (JAKs and possibly phosphatidylinositol 3-kinases) can phosphorylate sequence elements on the cytoplasmic domains (Jiang et al. 2005). Tyrosine-449 (Y449) in the cytoplasmic domain of Interleukin-7 receptor is required for T-cell development in vivo and for activation of the JAK/STAT5 and PI3K/Akt pathways (Jiang et al. 2004, Pallard et al. 1999).
It has been sugggested that JAK1 phosphorylates IL7R (Jiang et al. 2004) and it is believed that JAK3, associated with IL2RG, phosphorylates the tyrosine residues in the cytoplasmic portion of IL7R that lead to recruitment of STATs (Fry & Mackall 2002). This is consistent with the lack of intrinsic tyrosine kinase activity in IL7R:JAK1 in the absence of IL2RG:JAK3 (Lai et al. 1996).

Literature References

PubMed ID	Title	Journal	Year
26974155	LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors Cheng, Y, Wu, C, Tong, W, Zhang, H, Pei, D, Bhagat, A, Chikwava, K, Choi, JK	J. Clin. Invest.	2016
7719938	The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15 Bloom, ET, Mietz, J, Friedmann, M, John, S, Tsang, M, Yamauchi, A, Migone, TS, Lin, JX, Weatherbee, JA, Zhou, L	Immunity	1995