Phospho-IFNAR1 (Ser535) (F4V7F) Rabbit Monoclonal Antibody #37851

Interferon alpha/beta receptor 1 (IFNAR1) is one of the two protein subunits that comprise the type I interferon (IFN-I) surface receptor (1-4). IFNAR1 and IFNAR2 belong to the class II helical cytokine receptor (hCR) family, are ubiquitously expressed, and contain highly glycosylated extracellular domains, leading to high molecular weight by western blot (1-4,8). IFN-Is bind the IFN receptor, leading to the dimerization of IFNAR2 and IFNAR1 subunits, and the activation of Janus family kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways (2-5). All IFNαs bind IFNAR1 with a low affinity, and only IFNβ binds IFNAR1 with a relatively higher affinity (4,5). IFN-I signaling mediates various cellular responses, including antiviral responses, immunomodulatory responses, and antiproliferative effects (5). IFN-I signaling is being investigated as a therapeutic target for cancer, autoimmunity, sepsis, and viral infection (6,7).

Phosphorylation of IFNAR1, triggered by ligand binding and ligand-independent means, plays an important role in regulating IFN-I signaling. IFNAR1 phosphorylation at Ser535 leads to endocytosis and IFNAR1 degradation, leading to the decreased sensitivity of cells to subsequent cytokine stimulation (9-11). PKD2 phosphorylates IFNAR1 at Ser535 and is dependent on TYK2 catalytic activity in the ligand-induced pathway (10). In the ligand-independent pathway, IFNAR1 can be phosphorylated at Ser535 by CK1a (12).