Interleukin 13 Receptor, Alpha 1 (IL13RA1), also referred to as NR4 or CD213A1 (Cluster of Differentiation 213A1), is a subunit of the Interleukin 13 Receptor complex. The IL13RA1 gene encodes a precursor protein consisting of 427 amino acid (aa) residues. This includes a 21 aa residue signal peptide, a 324 aa residue extracellular domain, a 23 aa residue transmembrane region, and a 59 aa residue cytoplasmic tail.
IL13RA1 plays a crucial role in immune response by forming a receptor complex with the IL4 receptor alpha, a subunit common to both IL13 and IL4 receptors. As the primary IL13-binding subunit, IL13RA1 is integral to the IL13 receptor's function and may also contribute to the structure of IL4 receptors. The IL13RA1 protein has been demonstrated to bind with the tyrosine kinase TYK2, potentially mediating signaling pathways that activate JAK1, STAT3, and STAT6, which are induced by both IL13 and IL4.
Furthermore, IL13RA1 exhibits low-affinity binding to Interleukin-13 (IL13) and, in conjunction with the IL4 receptor alpha (IL4RA), forms a functional receptor for IL13. It also serves as an alternative accessory protein to the common cytokine receptor gamma chain (γc) in Interleukin-4 (IL4) signaling. However, it is important to note that IL13RA1 cannot replace the function of the Interleukin-2 Receptor Gamma (IL2RG) in enhancing Interleukin-2 (IL2) binding activity.
In the context of pancreatic cancer, IL-4 and IL-13 primarily exert their effects through their receptor heterodimers, IL-4 receptor alpha (IL-4Rα) and IL-13Rα1, collectively termed type II IL-4R. They activate signal transduction pathways including STAT3/6, IRS-ERK/PI3K-Akt, and mTOR, which are critical in the cellular response to these cytokines.