Identification of a gp130 Cytokine Receptor Critical Site Involved in Oncostatin M Response

Christophe Olivier, Patrick Auguste, Marie Chabbert, Eric Lelièvre, Sylvie Chevalier, Hugues Gascan
2000 Journal of Biological Chemistry  
Gp130 cytokine receptor is involved in the formation of multimeric functional receptors for interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor, and cardiotrophin-1. Cloning of the epitope recognized by an OSM-neutralizing anti-gp130 monoclonal antibody identified a portion of gp130 receptor localized in the EF loop of the cytokine binding domain. Site-directed mutagenesis of the corresponding region was carried out by alanine
more » ... on of residues 186 -198. To generate type 1 or type 2 OSM receptors, gp130 mutants were expressed together with either LIF receptor ␤ or OSM receptor ␤. When positions Val-189/Tyr-190 and Phe-191/Val-192 were alanine-substituted, Scatchard analyses indicated a complete abrogation of OSM binding to both type receptors. Interestingly, binding of LIF to type 1 receptor was not affected, corroborating the notion that in this case gp130 mostly behaves as a converter protein rather than a binding receptor. The present study demonstrates that positions 189 -192 of gp130 cytokine binding domain are essential for OSM binding to both gp130/LIF receptor ␤ and gp130/ OSM receptor ␤ heterocomplexes.
doi:10.1074/jbc.275.8.5648 pmid:10681548 fatcat:oxdx5dfhqrdtvmmhvz4f5zfv3q