Within the IL-2R complex JAK3 phosphorylates JAK1 Authored: Ray, KP, 2010-05-17 EC Number: 2.7.10 Edited: Jupe, S, 2010-08-06 Pubmed10825200 Pubmed10889465 Pubmed11750878 Pubmed7481768 Pubmed7568005 Pubmed7659163 Pubmed8022485 Pubmed8777722 Pubmed9382798 Pubmed9590172 Reactome Database ID Release 43451942 Reactome, http://www.reactome.org ReactomeREACT_27274 Receptor activation involves JAK1 and JAK3 as T-cells from mice lacking either kinase are unable to respond to cytokines that utilize the Common gamma chain (Rodig et al. 1998, Park et al. 1995). Naturally occurring JAK3 mutations prevent binding to the IL-2 receptor, leading to severe immunodeficiency due to a lack of IL2R signaling (Macchi et al. 1995, Russell et al. 1995). Mechanistic models of receptor activation suggest that assembly of the quaternary receptor and the consequent proximity of JAK1 and JAK3, bound to the cytoplasmic domains of the beta and gamma chains, is the trigger for JAK activation (Ellery et al. 2000). JAK3 is thought to activate JAK1, as JAK3 does not require tyrosine phosphorylation to activate its kinase activity (Liu et al. 1997), and JAK3 has been demonstrated to phosphorylate JAK1 in response to IL-2 (Kawahara et al. 1995). JAK3 also becomes phosphorylated in response to IL-2 (Johnston et al. 1994), either by JAK1 trans-activation or by an indirect mechanism. The activated JAKs then phosphorylate critical tyrosine residues within IL2RB. Reviewed: Dooms, H, 2011-03-17 Reviewed: Villarino, A, 2011-02-11 IL2:IL2R trimer:JAK1:JAK3 IL2:IL2R trimer:p-JAK1:JAK3