IL7RA is phosphorylated on Y449 Authored: Ray, KP, 2010-05-17 EC Number: 2.7.10.2 Edited: Jupe, S, 2011-05-06 IL7 receptor signaling is presumed to resemble that of other Gc family cytokines, based on detailed studies of the IL2 receptor. Extending this model to IL7 suggests a similar series of events that bring JAK1 and JAK3 into proximity within a complex IL7:IL7RA:JAK1:Gc:JAK3. Cytoplasmic domains of the IL7 receptor chains orient so that their associated kinases (Janus and possibly phosphatidylinositol 3-kinases) can phosphorylate sequence elements on the cytoplasmic domains (Jiang et al. 2005). <br><br>Tyr449 in the cytoplasmic domain of IL7RA 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). Phosphorylated Tyr449 is believed to be a docking site for STAT5 and possibly PI3K, which are then activated by JAKs (Lin et al. 1995, Jiang et al. 2004). T-cells from an IL7RA Y449F knock-in mouse did not activate STAT5 (Osbourne et al. 2007), indicating that IL7 regulates STAT5 activity via this key tyrosine. It is thought that JAK1 phosphorylates IL7RA (Jiang et al. 2004). Pubmed10367898 Pubmed15226449 Pubmed15996891 Pubmed17325202 Pubmed7719938 Reactome Database ID Release 431295519 Reactome, http://www.reactome.org ReactomeREACT_115749 Reviewed: Puck, J, 2011-11-03 IL7:IL7RA:JAK1:IL2RG:JAK3 IL7:p(Y449)-IL7RA:JAK1:IL2RG:JAK3