{"doi":"10.1074/jbc.274.46.33072","title":"Disulfide Linkage of Growth Hormone (GH) Receptors (GHR) Reflects GH-induced GHR Dimerization","abstract":null,"journal":"Journal of Biological Chemistry","year":1999,"id":591532,"datarank":3.3451633651258046,"base_score":4.634728988229636,"endowment":4.634728988229636,"self_citation_contribution":0.6952093482344455,"citation_network_contribution":2.649954016891359,"self_endowment_contribution":0.6952093482344455,"citer_contribution":2.649954016891359,"corpus_percentile":null,"corpus_rank":null,"citation_count":102,"citer_count":52,"citers_with_citation_signal":48,"citers_with_endowment":48,"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":1479193,"name":"Jing Jiang","orcid":"0000-0002-4169-8498","position":1,"is_corresponding":false},{"id":117548,"name":"John J. Kopchick","orcid":null,"position":2,"is_corresponding":false},{"id":118129,"name":"Stuart J. Frank","orcid":null,"position":3,"is_corresponding":false},{"id":603651,"name":"Yue Zhang","orcid":"0000-0001-6153-9833","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Disulfide Linkage of Growth Hormone (GH) Receptors (GHR) Reflects GH-induced GHR Dimerization","abstract":"The growth hormone (GH) receptor (GHR) binds GH in its extracellular domain and transduces activating signals via its cytoplasmic domain. Both GH-induced GHR dimerization and JAK2 tyrosine kinase activation are critical in initiation of GH signaling. We previously described a rapid GH-induced disulfide linkage of GHRs in human IM-9 cells. In this study, three GH-induced phenomena (GHR dimerization, GHR disulfide linkage, and enhanced GHR-JAK2 association) were examined biochemically and immunologically. By using the GH antagonist, G120K, and an antibody recognizing a dimerization-sensitive GHR epitope, we demonstrated that GH-induced GHR disulfide linkage reflects GH-induced GHR dimerization. GH, not G120K, promoted both GHR disulfide linkage and enhanced association with JAK2. Measures that diminished GH-dependent JAK2 and GHR tyrosine phosphorylation diminished neither GH-induced GHR disulfide linkage nor GH-enhanced GHR-JAK2 association. By using both transient and stable expression systems, we determined that cysteine 241 (an unpaired extracellular cysteine) was critical for GH-induced GHR disulfide linkage; however, GH-induced GHR dimerization, GHR-JAK2 interaction, and GHR, JAK2, and STAT5 tyrosine phosphorylation still proceeded when this cysteine residue was mutated. We conclude GH-induced GHR disulfide linkage is not required for GHR dimerization, and activation and GH-enhanced GHR-JAK2 association depends more on GHR dimerization than on GHR and/or JAK2 tyrosine phosphorylation.","is_dataset_classified":null,"base_score":4.634728988229636,"endowment":4.634728988229636,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10551877","pmcid":null,"openalex_id":"https://openalex.org/W2139573567","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"DK46395","title":null}],"total_grants":1,"fwci":3.1339,"citation_percentile":0.92116354,"influential_citations":0,"citation_trend":[{"year":2012,"count":6},{"year":2013,"count":1},{"year":2014,"count":4},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1074/jbc.274.46.33072","host_type":"journal"},{"url":"https://doi.org/10.1074/jbc.274.46.33072","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925817466166?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925817466166?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.274.46.33072","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10551877","host_type":"repository"}],"fields_of_study":["Growth Hormone and Insulin-like Growth Factors","Cancer, Hypoxia, and Metabolism","Lipid metabolism and disorders"],"mesh_terms":["Animals","Antibodies","Cell Line","Cysteine","Disulfides","DNA-Binding Proteins","Humans","Milk Proteins","Mutation","Peptide Fragments","Phosphorylation","Precipitin Tests","Protein-Tyrosine Kinases","Proto-Oncogene Proteins","Receptors, Somatotropin","Transfection","Trans-Activators","Dimerization","Human Growth Hormone","STAT5 Transcription Factor","Janus Kinase 2"],"keywords":["Growth hormone receptor","Disulfide Linkage","Tyrosine","Phosphorylation","Tyrosine phosphorylation","Chemistry","Tyrosine kinase","Receptor","Lysine","Internal medicine","Biochemistry","Cysteine","Endocrinology","Biology","Growth hormone","Amino acid","Hormone","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-25T17:24:48.418786Z","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":[]}