or 
Receptor Family
Cytokine Type 2 receptors
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Summary

This family includes receptors for interferon-gamma (IFN- ), IFN- , interleukin-10, and coagulation protease factor VII (tissue factor). There are two types of interferons. IFN- is the only type II interferon, whereas the type I interferons comprise four major classes: IFN- , IFN- , IFN- , and IFN- . Competitive ligand binding studies have shown that type I IFNs share the same receptor complex whereas type II IFN (IFN- ) binds to a distinct type II receptor. IFN- is a lymphokine produced by activated T lymphocytes and natural killer cells. It signals through a receptor complex consisting of two different but structurally-related transmembrane chains: the high-affinity receptor-binding subunit (IFN- -R- ) and an accessory factor called AF-1 or IFN- -R- . The extracellular IFN- -R- -chain has two fibronectin type-III-like domains and two immunoglobulin-like domains that are responsible for IFN- binding. In the signalling complex, the two chains interact through their extracellular domains. Crystal structure analysis revealed that one IFN- homodimer binds the receptor heterodimer. Upon ligand binding to the high-affinity receptor unit, conformational changes in both the ligand homodimer and the receptor heterodimer allow an 'induced fit' that results in the formation of the final complex. Type I IFNs bind to a receptor composed of two transmembrane polypeptides, IFNAR1 and IFNAR2. This ligand-receptor interaction is less characterized than the type II interactions. Antibodies to human IFN-R1 block the activity of various type I interferons, indicating that the human IFN- R1 molecule is one component of the type I IFN receptor. Binding of type I interferons to their receptors induces tyrosine phosphorylation of multiple intracellular proteins including the and subunits of the receptor, the polypeptides that form the transcriptional activator ISGF3 (Stat113, Stat84, and Stat91), and the p135tyk2 and Jak-1 tyrosine kinases. Related to the IFN receptors, the IL-10 receptor has a ligand-binding subunit (IL-10R1) and an accessory signalling subunit, IL-10R2. Similar to IFN- , IL-10 binds with high affinity to its receptor unit 1 whereas receptor unit 2 recruits Tyk2 into the signalling complex. Unlike IL-10, its homolog IL-22 signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4. A related protein, designated IL-22RA2, is a naturally expressed soluble IL-22 antagonist that represents a further level of regulation in this family of receptors. Renauld (2003) reviewed these receptors and their ligands in deapth.
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