{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Luo H"],"funding":["Canadian Institutes of Health Research"],"pagination":["44976-87"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3247986"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["286(52)"],"pubmed_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."],"journal":["The Journal of biological chemistry"],"pubmed_title":["Ephrinb1 and Ephrinb2 are associated with interleukin-7 receptor α and retard its internalization from the cell surface."],"pmcid":["PMC3247986"],"funding_grant_id":["MOP97829","MOP57697","MOP69089"],"pubmed_authors":["Wu Z","Wu J","Jin W","Han B","Luo H","Qi S"],"additional_accession":[]},"is_claimable":false,"name":"Ephrinb1 and Ephrinb2 are associated with interleukin-7 receptor α and retard its internalization from the cell surface.","description":"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.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Dec","modification":"2022-02-09T12:27:37.201Z","creation":"2019-03-27T00:47:27Z"},"accession":"S-EPMC3247986","cross_references":{"pubmed":["22069310"],"doi":["10.1074/jbc.m111.316414","10.1074/jbc.M111.316414"]}}