N-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2.

N-Glycosylation Regulates Chitinase 3-like-1 and IL-13 Ligand Binding to IL-13 Receptor α2. Am J Respir Cell Mol Biol. 2020 May 13;: Authors: He CH, Lee CG, Ma B, Kamle S, Choi AMK, Elias JA Abstract Chitinase 3-like-1 (Chi3l1) and IL-13 are both ligands of IL-13 receptor α2 (IL-13Rα2). The binding of the former activates MAPK, AKT and Wnt/β-catenin signaling and plays important roles in innate and adaptive immunity, cellular apoptosis, oxidative injury, allergic inflammation, tumor metastasis and wound healing, fibrosis and repair in the lung. In contrast, the latter binding is largely a decoy event that diminishes the effects of IL-13. Here we demonstrate that IL-13Rα2 N-glycosylation is a critical determinant of which ligand binds. Structure function evaluations demonstrated that Chi3l1-IL-13Rα2 binding was increased when sites of N-glycosylation are mutated and studies with tunicamycin and PNGase F demonstrated that Chi3l1-IL-13Rα2 binding and signaling were increased when N-glycosylation was diminished. In contrast, structure function experiments demonstrated that IL-13 binding to IL-13Rα2 was dependent on each of the 4 sites of N-glycosylation in IL-13Rα2 and experiments with tunicamycin and PNGase F demonstrated that IL-13-IL-13Rα2 binding was decreased when IL-13Rα2 N-glycosylation was diminished. Studies with primary lung epithelial cells also demonstrated that Chi3l1 inhibited while IL-13 stimulated the catalytic...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research