|Detection of Human IFN‑ alpha / beta R2 by Western Blot. Western blot shows lysates of K562 human chronic myelogenous leukemia cell line. PVDF Membrane was probed with 1 µg/mL of Human IFN‑ alpha / beta R2 Antigen Affinity-purified Polyclonal Antibody (Catalog # AF4015) followed by HRP-conjugated Anti-Goat IgG Secondary Antibody (Catalog # HAF019). A specific band was detected for IFN‑ alpha / beta R2 at approximately 58 kDa (as indicated). This experiment was conducted under reducing conditions and using Immunoblot Buffer Group 1.|
IFN-alpha / beta R2, also known as IFNAR2, is a 100 kDa glycoprotein in the class II cytokine receptor family. These proteins form heterodimeric receptor complexes that transduce signals from the interferon, IL-10, and IL-28 families of cytokines (1, 2). IFN-alpha / beta R2, in association with IFN-alpha / beta R1, is required for mediating the antiviral, antiproliferative, and apoptotic effects of the type I interferons IFN-alpha and IFN-beta. IFN-alpha / beta R2 is the principal ligand binding subunit of the receptor. Ligand binding is stabilized by the subsequent association with IFN-alpha / beta R1, resulting in the formation of a signaling ternary receptor complex (3, 4). Mature human IFN-alpha / beta R2 consists of a 217 amino acid (aa) extracellular domain (ECD) with two fibronectin type III repeats, a 21 aa transmembrane segment, and a 251 aa cytoplasmic domain. Alternate splicing generates a secreted isoform that corresponds to the ECD and a 50 kDa transmembrane isoform with a substituted and truncated cytoplasmic region (5, 6). The short isoform is impaired in its ability to activate signaling molecules and functions as a dominant negative receptor subunit (7-9). IFN-alpha / beta R2 is also subject to presenilin-dependent intramembrane proteolysis, resulting in the liberation of nearly the entire ECD as well as the cytoplasmic domain which migrates to the nucleus and can inhibit gene transcription (10). High concentrations of soluble IFN-alpha / beta R2 bind and neutralize IFN-alpha and IFN-beta, while lower concentrations prolong the antiviral activity of circulating IFN-beta but not IFN-alpha (11). Human but not mouse IFN-alpha / beta R2 constitutively associates with STAT4, which may account for species specific differences observed in type I interferon responses (12). Within the ECD, human IFN-alpha / beta R2 shares 63%, 60%, and 48% aa sequence identity with bovine, mouse, and ovine IFN-alpha / beta R2, respectively.
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