Identification of a domain in the β subunit of the type I interferon (IFN) receptor that exhibits a negative regulatory effect in the growth inhibitory action of type I IFNs

Expression of human α and long form of the β (β(L)) subunits of type I interferon receptor (IFN-R) in mouse cells is sufficient to activate the Jak-Stat pathway and to elicit an antiviral state in response to human IFNα2 and IFNβ. We demonstrate herein, however, that these cells respond to the antiproliferative effects of murine IFNαβ but not human type I IFNs. These results suggest that an unknown species-specific component is required for the antiproliferative effect of human type I IFNs. The absence of this component can be complemented by expressing the human β(L) chain truncated at amino acid 346. Thus, the distal region of β(L) appears to function as a negative regulator of the growth inhibitory effects of type I IFNs. Further studies looking for possible targets of the β(L) regulatory domain demonstrated that this region associates with a tyrosine phosphatase. These results suggest that a protein associated with the negative N regulatory domain of β(L), likely a tyrosine phosphatase, plays a role in regulating the growth inhibitory effects of human type I IFNs.