1. Respirovirus C protein inhibits activation of type I interferon receptor‐associated kinases to block JAK‐STAT signaling
- Author
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Miki Kohno, Mayu Yamaguchi, Yoshinori Kitagawa, Bin Gotoh, Madoka Sakai, and Masae Itoh
- Subjects
food.ingredient ,Protein subunit ,Biophysics ,Receptor, Interferon alpha-beta ,Respirovirus ,Sendai virus ,Biochemistry ,Cell Line ,JAK-STAT pathway ,Viral Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,food ,Structural Biology ,Interferon ,Genetics ,medicine ,Humans ,Phosphorylation ,Molecular Biology ,030304 developmental biology ,TYK2 Kinase ,0303 health sciences ,respirovirus ,biology ,Kinase ,030302 biochemistry & molecular biology ,Tyrosine phosphorylation ,Janus Kinase 1 ,interferon ,Cell Biology ,C protein ,TYK2 ,biology.organism_classification ,Cell biology ,STAT Transcription Factors ,HEK293 Cells ,JAK1 ,chemistry ,Tyrosine kinase 2 ,Mutation ,Signal Transduction ,medicine.drug - Abstract
Respirovirus C protein blocks the type I interferon (IFN)-stimulated activation of the JAK-STAT pathway. It has been reported that C protein inhibits IFN-α-stimulated tyrosine phosphorylation of STATs, but the underlying mechanism is poorly understood. Here, we show that the C protein of Sendai virus (SeV), a member of the Respirovirus genus, binds to the IFN receptor subunit IFN-α/β receptor subunit (IFNAR)2 and inhibits IFN-α-stimulated tyrosine phosphorylation of the upstream receptor-associated kinases, JAK1 and TYK2. Analysis of various SeV C mutant (Cm) proteins demonstrates the importance of the inhibitory effect on receptor-associated kinase phosphorylation for blockade of JAK-STAT signaling. Furthermore, this inhibitory effect and the IFNAR2 binding capacity are observed for all the respirovirus C proteins examined. Our results suggest that respirovirus C protein inhibits activation of the receptor-associated kinases JAK1 and TYK2 possibly through interaction with IFNAR2.
- Published
- 2019