IDENTIFICATION OF A DOMAIN IN THE BETA-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 alpha and long form of the beta (beta(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 res ponse to human IFN alpha 2 and IFN beta. We demonstrate herein, howeve r, that these cells respond to the antiproliferative effects of murine IFN alpha beta but not human type I IFNs. These results suggest that an unknown species-specific component is required for the antiprolifer ative effect of human type I IFNs. The absence of this component can b e complemented by expressing the human beta(L) chain truncated at amin o acid 346, Thus, the distal region of beta(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 beta(L), regulator y domain demonstrated that this region associates with a tyrosine phos phatase. These results suggest that a protein associated with the nega tive regulatory domain of beta(L), likely a tyrosine phosphatase, play s a role in regulating the growth inhibitory effects of human type I I FNs.