IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3 binds PI3K regulatory subunits

Stable Identifier
R-HSA-1295516
Type
Reaction
Species
Homo sapiens
Compartment
Synonyms
p85 binds p(Y449)-IL7RA
Locations in the PathwayBrowser
Summation

Inferred from mouse:
The p85 subunit of PI3-kinase (PI3K) binds to phosphorylated Tyrosine-449 (Y449) on IL7R.
Y449F substitution inhibits PI3K-dependent proliferation of IL7-stimulated murine B-lineage cells (Venkitaraman & Cowling 1994). Stimulation of human lymphocyte precursor cells with IL7 induced tyrosine phosphorylation of the p85 subunit of 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. 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).

Rochman et al. (2009) suggested 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 inhibiting the expression of pro-apoptotic factors BAX and BAD.
Interleukin-7 induced PI3K-dependent phosphorylation of AKT1 (Akt1 or PKB) and its downstream targets GSK-3, FOXO1, and FOXO3a (Barata et al.2004).

Literature References
PubMed ID Title Journal Year
15353558 Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells

Barata, JT, Silva, A, Brandao, JG, Nadler, LM, Cardoso, AA, Boussiotis, VA

J. Exp. Med. 2004
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