Recombinant Human IL-31RA Fc Chimera Protein, CF

The interleukin-31 receptor A subunit (IL-31 RA), also known as gp130-Like Monocyte Receptor (GLM-R or GPL), is a ~100 kDa type I transmembrane glycoprotein that is classified as being a type I cytokine receptor (1, 2). A heterodimeric complex of IL-31 RA and the oncostatin M receptor (OSM-R) functions as the signaling receptor for IL-31 (3). Both subunits are inducibly expressed throughout the myelomonocytic lineage and are upregulated by interferon-gamma and bacterial lipopolysaccharides (1-3). IL-31 RA is also expressed on keratinocytes, dorsal root ganglia neurons, and variably on lung epithelial cells (3-6). The 732 amino acid (aa) IL-31 RA contains a 19 aa signal sequence, a 500 aa extracellular domain (ECD), a 21 aa transmembrane domain and a 192 aa cytoplasmic domain. The ECD shares 60%, 58%, 73% and 70% aa identity with mouse, rat, canine and bovine IL-31 RA ECD, respectively. Human IL-31 receptors do not respond to mouse IL-31 (7). The ECD contains five fibronectin type III domains; the first two contain four conserved cysteine residues and a WSXWS motif common to type I cytokine receptors (2). Twelve alternately spliced human IL-31 RA isoforms are known and range in size from 356-745 amino acids. A long (745 aa) and a short (560 aa) transmembrane form are the predominant forms, and many cell lines express both forms (8). The long form, like the 732 aa form, signals by recruiting STAT3, 5 or 1, while the short form does not recruit STATs and inhibits IL-31 signaling. The ratio of these forms and their co-expression with OSM-R determines a cell's response to IL-31 (8). In both humans and transgenic mice, IL-31 from skin-homing Th2 cells may contribute to the pruritis (itching) associated with nonatopic dermatitis, especially in infected skin (3, 9, 10).