Interleukin-7 receptor (IL7R) has a small juxta-membrane region known as the Box1 motif, which is conserved throughout the type 1 cytokine receptor family (Murakami et al. 1991) and believed to be the site of JAK1 binding (Tanner et al. 1995). Deletion of the Box1 region of IL7R eliminates JAK1 phosphorylation (Jiang et al. 2004). Studies using mutant Interleukin-4/Interleukin-7 chimeric receptors found that loss of Box1 resulted in rapid cell death, while Y449F mutation causes cell cycle arrest that precedes cell death (Jiang et al. 2004). Mice expressing a knock-in mutation (IL7R Y449F) displayed defective homeostatic proliferation of naive CD4 and CD8 T-cells (Osbourne et al. 2007). The Y449 site is thus of particular interest because two critical Interleukin-7 signaling pathways, the JAK/STAT pathway and the phosphatidylinositol 3-kinase (PI3K)/AKT pathway may originate from this site (Pallard et al. 1999).