p85 binds p(Y449)-IL7RA Authored: Ray, KP, 2010-05-17 Edited: Jupe, S, 2011-05-06 Pubmed10367898 Pubmed15123689 Pubmed18523275 Pubmed19543225 Pubmed7520779 Pubmed7522165 Reactome Database ID Release 431295516 Reactome, http://www.reactome.org ReactomeREACT_115826 Reviewed: Puck, J, 2011-11-03 The p85 subunit of PI3K binds to phosphorylated Tyr-449 on IL7RA; Y449F substitution inhibits PI3K-dependent proliferation of IL7-stimulated murine B-lineage cells (Venkitaraman & Cowling 1994).<br><br>Stimulation of human lymphocyte precursor cells with IL-7 induced tyrosine phosphorylation of the p85 subunit of PI3-kinase (PI3K) and activation of PI3K kinase activity (Dadi et al. 1994). It is thought that, depending on species differences and stage of lymphocyte development, IL7 induced PI3K pathway can promote signals that are important for survival and proliferation of both T cells and B cells. <br><br>Activation of PI3K leads to the generation of membrane associated PIP3 and membrane recruitment of AKT/PKB, the key downstream target of PI3K. AKT mediates phosphorylation of downstream substrates involved in regulation of cell survival and proliferation. IL7 induced activation of PI3K/AKT in human thymocytes has been reported (Pallard et al. 1999; Johnson et al. 2008). In mouse thymocytes IL7 stimulation resulted in the inactivation of BAD by serine phosphorylation; the PI3K/AKT pathway has been implicated in BAD phosphorylation. These results suggest that IL7 signaling via AKT inactivates the pro-apoptotic protein BAD promoting T cell survival (Li et al. 2004). <br><br>Rochman et al. (2009) suggest that IL7 promotes lymphocyte survival by activating the pro-survival PI3K/AKT signaling pathway and by increasing the expression of survival factors such as BCL2 and myeloid cell leukemia sequence 1 (MCL-1) while iinhibiting the expression of pro-apoptotic factors BAX and BAD. PI3K-regulatory subunits IL7:p(Y449)-IL7RA:JAK1:IL2RG:JAK3:PI3K-regulatory subunits IL7:p(Y449)-IL7RA:JAK1:IL2RG:JAK3