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The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression
Author(s) -
Ragimbeau Josiane,
Dondi Elisabetta,
Alcover Andrés,
Eid Pierre,
Uzé Gilles,
Pellegrini Sandra
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg038
Subject(s) - biology , tyrosine kinase 2 , microbiology and biotechnology , endocytosis , receptor , cell surface receptor , endosome , tyrosine kinase , receptor tyrosine kinase , janus kinase , signal transduction , biochemistry , platelet derived growth factor receptor , growth factor
The four mammalian Jak tyrosine kinases are non‐covalently associated with cell surface receptors binding helical bundled cytokines. In the type I interferon receptor, Tyk2 associates with the IFNAR1 receptor subunit and positively influences ligand binding to the receptor complex. Here, we report that Tyk2 is essential for stable cell surface expression of IFNAR1. In the absence of Tyk2, mature IFNAR1 is weakly expressed on the cell surface. Rather, it is localized into a perinuclear endosomal compartment which overlaps with that of recycling transferrin receptors and with early endosomal antigen‐1 (EEA1) positive vesicles. Conversely, co‐expressed Tyk2 greatly enhances surface IFNAR1 expression. Importantly, we demonstrate that Tyk2 slows down IFNAR1 degradation and that this is due, at least in part, to inhibition of IFNAR1 endocytosis. In addition, Tyk2 induces plasma membrane relocalization of the R2 subunit of the interleukin‐10 receptor. These results reveal a novel function of a Jak protein on internalization of a correctly processed cytokine receptor. This function is distinct from the previously reported effect of other Jak proteins on receptor exit from the endoplasmic reticulum.