title: Ephrinb1 and Ephrinb2 are associated with interleukin-7 receptor α and retard its internalization from the cell surface.
abstract: IL-7 plays vital roles in thymocyte development, T cell homeostasis, and the survival of these cells. IL-7 receptor α (IL-7Rα) on thymocytes and T cells is rapidly internalized upon IL-7 ligation. Ephrins (Efns) are cell surface molecules and ligands of the largest receptor kinase family, Eph kinases. We discovered that T cell-specific double gene knock-out (dKO) of Efnb1 and Efnb2 in mice led to reduced IL-7Rα expression in thymocytes and T cells, and that IL-7Rα down-regulation was accelerated in dKO CD4 cells upon IL-7 treatment. On the other hand, Efnb1 and Efnb2 overexpression on T cell lymphoma EL4 cells retarded IL-7Rα down-regulation. dKO T cells manifested compromised STAT5 activation and homeostatic proliferation, an IL-7-dependent process. Fluorescence resonance energy transfer and immunoprecipitation demonstrated that Efnb1 and Efnb2 interacted physically with IL-7Rα. Such interaction likely retarded IL-7Rα internalization, as Efnb1 and Efnb2 were not internalized. Therefore, we revealed a novel function of Efnb1 and Efnb2 in stabilizing IL-7Rα expression at the post-translational level, and a previously unknown modus operandi of Efnbs in the regulation of expression of other vital cell surface receptors.
authors: Laboratory of Immunology, Centre Hospitalier de l'Université deMontréal, Montreal, Quebec H2L 4M1, Canada.
authors: Hongyu
authors: H
authors: Luo
authors: Zenghui
authors: Z
authors: Wu
authors: Shijie
authors: S
authors: Qi
authors: Wei
authors: W
authors: Jin
authors: Bing
authors: B
authors: Han
authors: Jiangping
authors: J
authors: Wu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D036387:Ephrin-B1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D036388:Ephrin-B2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D055550:Protein Stability; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D036388:Ephrin-B2; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor