Formation of a uniquely stable type I interferon receptor complex by interferon beta is dependent upon particular interactions between interferon beta and its receptor and independent of tyrosine phosphorylation

Human type I interferons (IFN) require two receptor chains, IFNAR1 and IFNA R2c for high affinity (pM) binding and biological activity. Our previous st udies have shown that the ligand dependent assembly of the type I IFN recep tor chains is not identical for all type I IFNs. IFN beta appears unique in its ability to assemble a stable complex of receptor chains, as demonstrat ed by the observation that IFNAR2c co-immunoprecipitates with IFNAR1 when c ells are stimulated with IFN beta but not with IFN alpha. The characteristi cs of such a receptor complex are not well defined nor is it understood if differential signaling events can be mediated by variations in receptor ass embly. To further characterize the factors required for formation of such a stable receptor complex we demonstrate using IFN stimulated Daudi cells th at (1) IFNAR2c coimmunoprecipitates with IFNAR1 even when tyrosine phosphor ylation of receptor chains is blocked with staurosporine, and (2) IFN beta 1b but not IFN alpha 2, is present in the immunoprecipitated receptor compl ex. These results demonstrate that the unique IFN beta induced assembly of type I IFN receptor chains is independent of receptor tyrosine phosphorylat ion and the recruitment of additional proteins to the receptor by such even ts. Furthermore, the presence of IFN beta 1b in the immunoprecipitated IFN receptor complex suggests that IFN beta interacts and binds differently to the receptor than IFN alpha 2. These results suggest that the specific asse mbly of type I IFN receptor chains is ligand dependent and may represent an early event which leads to the differential biological responses observed among type I IFNs. (C) 1999 Academic Press.