Interferon alpha/beta receptor 1 (IFNalpha/beta R1), also known as IFNAR1, is a 100130kD member of the class II cytokine receptor family of proteins. These proteins form heterodimeric receptor complexes that mediate class II cytokine signals. Subunits of the different receptor complexes are shared and serve multiple functions (1). IFNalpha/beta R1, in association with IFNalpha/beta R2, is required for propagating antimicrobial signal transduction triggered by the type 1 interferons such as IFNalpha and IFNbeta (2, 3). Mature human IFNalpha/beta R1 consists of a 409 aa extracellular domain (ECD), a 21 aa transmembrane segment, and a 100 aa cytoplasmic domain (4). The ECD contains three tandem fibronectin type III repeats and is extensively glycosylated. Within the ECD, human IFNalpha/beta R1 shares 47% and 50% aa identity with mouse and rat IFNalpha/beta R1, respectively. Alternative splicing generates two additional isoforms that lack the transmembrane segment and either all or a portion of the cytoplasmic domain. IFNalpha/beta R1 interacts very weakly or not at all with type 1 interferons and does not stably interact with IFNalpha/beta R2. Ligands preferentially associate with IFNalpha/beta R2, and this complex subsequently forms a stable ternary assembly with IFNalpha/beta R1 (57). IFNalpha/beta R1 also associates with IFNgamma R2 even in the absence of IFNgamma stimulation (3). IFNalpha/beta R1 activation depends on tyrosine phoshorylation as well as palmitoylation of its cytoplasmic domain (8, 9). Rapid downregulation of the receptor is accomplished by liganddependent or independent pathways (e.g. VEGF R signaling, TLR signaling, or cellular stress) which induce its serine phosphorylation, ubiquitination, and degradation (1013).
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