A REGION OF THE BETA-SUBUNIT OF THE INTERFERON-ALPHA 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 alpha and beta(L) subunits of the human interferon alpha (IFN alpha) receptor is required for the induction of an antivi ral state by human IFN alpha. To explore the role of the different dom ains of the beta(L) subunit in IFN alpha signaling, we coexpressed wil d-type alpha subunit and truncated forms of the beta(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 beta(L) chain are suffic ient to activate the Jak-Stat pathway and trigger an antiviral state a fter IFN alpha 2 binding to the receptor. This region of the beta(L) c hain, required for Jak1 binding and activation, contains the Bos 1 mot if that is important; for the interaction of some cytokine receptors w ith Jak kinases, However, using glutathione S-transferase fusion prote ins containing amino-and carboxyl-terminal deletions of the beta(L) cy toplasmic domain, we demonstrate that the main Jak1-binding region (co rresponding to AAs 300-346 on the beta subunit) is distinct from the B ox 1 domain (AAs 287-295).