{"doi":"10.4049/jimmunol.162.3.1480","title":"Activation of the Signal Transducer Glycoprotein 130 by Both IL-6 and IL-11 Requires Two Distinct Binding Epitopes","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The coordination and regulation of immune responses are primarily mediated by cytokines that bind to specific cell surface receptors. Glycoprotein 130 (gp130) belongs to the family of class I cytokine receptors and is the common signal-transducing receptor subunit shared by the so-called IL-6 type cytokines (IL-6, IL-11, ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M, and cardiotrophin-1). The inflammatory cytokines IL-6 and IL-11 induce gp130 homodimerization after binding to their specific α receptors, which leads to the activation of the Janus kinase/STAT signal transduction pathway. A molecular model of IL-6/IL-6R/gp130, which is based on the structure of the growth hormone/growth hormone receptor complex, allowed the selection of several amino acids located in the cytokine-binding module of gp130 for mutagenesis. The mutants were analyzed with regard to IL-6- or IL-11-induced STAT activation and ligand binding. It was found that Y190 and F191 are essential for the interaction of gp130 with IL-6 as well as IL-11, suggesting a common mode of recognition of helical cytokines by class I cytokine receptors. Furthermore, the requirement of the gp130 N-terminal Ig-like domain for ligand binding and signal transduction was demonstrated by the use of deletion mutants. Thus, besides the observed analogy to the growth hormone/growth hormone receptor complex, there is a substantial difference in the mechanism of receptor engagement by cytokines that signal via gp130.</jats:p>","journal":"The Journal of Immunology","year":1999,"id":670858,"datarank":3.4149400675392334,"base_score":4.418840607796598,"endowment":4.418840607796598,"self_citation_contribution":0.6628260911694899,"citation_network_contribution":2.7521139763697433,"self_endowment_contribution":0.6628260911694899,"citer_contribution":2.7521139763697433,"corpus_percentile":null,"corpus_rank":null,"citation_count":82,"citer_count":60,"citers_with_citation_signal":54,"citers_with_endowment":54,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1752488,"name":"Ursula Horsten","orcid":null,"position":1,"is_corresponding":false},{"id":1752490,"name":"Stefan Pflanz","orcid":null,"position":2,"is_corresponding":false},{"id":625521,"name":"Heike Dahmen","orcid":"0000-0003-4430-9889","position":3,"is_corresponding":false},{"id":1752491,"name":"Andrea Küster","orcid":null,"position":4,"is_corresponding":false},{"id":1752492,"name":"Joachim Grötzinger","orcid":null,"position":5,"is_corresponding":false},{"id":1752493,"name":"Peter C Heinrich","orcid":null,"position":6,"is_corresponding":false},{"id":1752494,"name":"Gerhard Müller-Newen","orcid":null,"position":7,"is_corresponding":false},{"id":28482,"name":"Ingo Kurth","orcid":"0000-0002-5642-8378","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Activation of the Signal Transducer Glycoprotein 130 by Both IL-6 and IL-11 Requires Two Distinct Binding Epitopes","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The coordination and regulation of immune responses are primarily mediated by cytokines that bind to specific cell surface receptors. Glycoprotein 130 (gp130) belongs to the family of class I cytokine receptors and is the common signal-transducing receptor subunit shared by the so-called IL-6 type cytokines (IL-6, IL-11, ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin M, and cardiotrophin-1). The inflammatory cytokines IL-6 and IL-11 induce gp130 homodimerization after binding to their specific α receptors, which leads to the activation of the Janus kinase/STAT signal transduction pathway. A molecular model of IL-6/IL-6R/gp130, which is based on the structure of the growth hormone/growth hormone receptor complex, allowed the selection of several amino acids located in the cytokine-binding module of gp130 for mutagenesis. The mutants were analyzed with regard to IL-6- or IL-11-induced STAT activation and ligand binding. It was found that Y190 and F191 are essential for the interaction of gp130 with IL-6 as well as IL-11, suggesting a common mode of recognition of helical cytokines by class I cytokine receptors. Furthermore, the requirement of the gp130 N-terminal Ig-like domain for ligand binding and signal transduction was demonstrated by the use of deletion mutants. Thus, besides the observed analogy to the growth hormone/growth hormone receptor complex, there is a substantial difference in the mechanism of receptor engagement by cytokines that signal via gp130.</jats:p>","is_dataset_classified":null,"base_score":4.418840607796598,"endowment":4.418840607796598,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9973404","pmcid":null,"openalex_id":"https://openalex.org/W1573665547","authors":[],"funders":[],"total_grants":0,"fwci":3.3012,"citation_percentile":0.92473068,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2014,"count":2},{"year":2015,"count":4},{"year":2016,"count":3},{"year":2017,"count":1},{"year":2020,"count":2},{"year":2021,"count":4},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":3}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/162/3/1480/1098138/im039901480o.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/162/3/1480/1098138/im039901480o.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/162/3/1480/62757732/im039901480o.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.162.3.1480","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9973404","host_type":"repository"}],"fields_of_study":["Cytokine Signaling Pathways and Interactions","Medicinal Plant Pharmacodynamics Research","Pharmacological Effects of Natural Compounds"],"mesh_terms":["Animals","Epitopes","Binding Sites","Humans","Membrane Glycoproteins","Models, Molecular","Protein Conformation","Signal Transduction","Antigens, CD","Interleukin-6","Mutagenesis, Site-Directed","Interleukin-11","Receptors, Interleukin","COS Cells","Receptors, Interleukin-6","Macromolecular Substances","Cytokine Receptor gp130","Receptors, Interleukin-11","Interleukin-11 Receptor alpha Subunit"],"keywords":["Glycoprotein 130","Oncostatin M","Janus kinase 1","Leukemia inhibitory factor","Biology","Cell biology","Cytokine receptor","Receptor","Signal transduction","Janus kinase","Leukemia inhibitory factor receptor","Interleukin-6 receptor","Common gamma chain","Cytokine","Interleukin-21 receptor","Molecular biology","Biochemistry","Interleukin","Interleukin 6","Immunology","STAT3"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T00:17:33.831274Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}