Identification of a gp130 cytokine receptor critical site involved in oncostatin M response.
J Biol Chem
; 275(8): 5648-56, 2000 Feb 25.
Article
de En
| MEDLINE
| ID: mdl-10681548
ABSTRACT
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 substitution of residues 186-198. To generate type 1 or type 2 OSM receptors, gp130 mutants were expressed together with either LIF receptor beta or OSM receptor beta. 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 beta and gp130/OSM receptor beta heterocomplexes.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Peptides
/
Glycoprotéines membranaires
/
Antigènes CD
/
Cytokines
/
Lymphokines
/
Interleukine-6
/
Inhibiteurs de croissance
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
Limites:
Animals
/
Humans
Langue:
En
Journal:
J Biol Chem
Année:
2000
Type de document:
Article
Pays d'affiliation:
France