A region of the β subunit of the interferon α receptor different from Box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state

Coexpression of the α and β(L) subunits of the human interferon α (IFNα) receptor is required for the induction of an antiviral state by human IFNα. To explore the role of the different domains of the β(L) subunit in IFNα signaling, we coexpressed wild-type α subunit and truncated forms of the β(L) chain in L-929 cells. Our results demonstrated that the first 82 amino acids (AAs) (AAs 265-346) of the cytoplasmic domain of the β(L) chain are sufficient to activate the Jak-Stat pathway and trigger an antiviral state after IFNα2 binding to the receptor. This region of the β(L) chain, required for Jak1 binding and activation, contains the Box 1 motif that is important for the interaction of some cytokine receptors with Jak kinases. However, using glutathione S-transferase fusion proteins containing amino- and carboxyl-terminal deletions of the β(L) cytoplasmic domain, we demonstrate that the main Jak1-binding region (corresponding to AAs 300-346 on the β subunit) is distinct from the Box 1 domain (AAs 287-295).