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

Stable Identifier
R-HSA-8983063
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
Synonyms
JAK3 is phosphorylated after IL7:IL7R binding
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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
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

Lin, JX, Migone, TS, Tsang, M, Friedmann, M, Weatherbee, JA, Zhou, L, Yamauchi, A, Bloom, ET, Mietz, J, John, S

Immunity 1995
26974155 LNK/SH2B3 regulates IL-7 receptor signaling in normal and malignant B-progenitors

Cheng, Y, Chikwava, K, Wu, C, Zhang, H, Bhagat, A, Pei, D, Choi, JK, Tong, W

J. Clin. Invest. 2016
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
transmembrane receptor protein kinase activity of IL7:IL7R:JAK1:IL2RG:JAK3 [plasma membrane]
Physical Entity
Activity
Orthologous Events
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Reviewed
Created