Two type1 membrane proteins belonging to the hemopoietin receptor family have been cloned and shown to bind IL-13 with differing affinities. The lower affinity IL-13 binding protein, previously designated IL-13 R alpha, IL-13 R alpha ' or NR4, is now referred to as IL-13 R alpha 1. The high affinity IL-13 binding protein, previously also designated IL-13 R or IL-13 R alpha ', is now referred to as IL-13 R alpha 2.
The mouse IL-13 R alpha 2 cDNA encodes a 383 amino acid (aa) residue precursor protein with a putative 21 aa residue signal peptide, a 313 residue extracellular domain, a 22 aa residue transmembrane region, and a 27 aa residue cytoplasmic tail. Human and mouse IL-13 R alpha 2 share 59% aa sequence identity. The extracellular domain of IL-13 R alpha 2 is also closely related to that of IL-13 R alpha 1. However, the cytoplasmic domain of IL-13 R alpha 2 lacks the box 1 and box 2 signaling motif and is much shorter than that of IL-13 R alpha 1, suggesting that the two receptors are functionally distinct. IL-13 R alpha 1 has been shown to combine with IL-4 R alpha to form a high-affinity receptor complex capable of transducing both an IL-4-dependent and an IL-13-dependent proliferative signal. The role of IL-13 R alpha 2 in IL-13 signaling remains to be elucidated. The amino-terminal 27 amino acid residues of mouse IL-13 R alpha 2 are identical to that of a soluble mouse IL-13 binding protein purified from mouse serum and urine. Recombinant mouse IL-13 R alpha /Fc chimera has been shown to bind IL-13 with high affinity and is a potent IL-13 antagonist.
