{"doi":"10.1126/science.aaw3242","title":"Mechanism of homodimeric cytokine receptor activation and dysregulation by oncogenic mutations","abstract":"Homodimeric class I cytokine receptors are assumed to exist as preformed dimers that are activated by ligand-induced conformational changes. We quantified the dimerization of three prototypic class I cytokine receptors in the plasma membrane of living cells by single-molecule fluorescence microscopy. Spatial and spatiotemporal correlation of individual receptor subunits showed ligand-induced dimerization and revealed that the associated Janus kinase 2 (JAK2) dimerizes through its pseudokinase domain. Oncogenic receptor and hyperactive JAK2 mutants promoted ligand-independent dimerization, highlighting the formation of receptor dimers as the switch responsible for signal activation. Atomistic modeling and molecular dynamics simulations based on a detailed energetic analysis of the interactions involved in dimerization yielded a mechanistic blueprint for homodimeric class I cytokine receptor activation and its dysregulation by individual mutations.","journal":"Science","year":2020,"id":50478,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":191,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":248026,"name":"Maximillian Hafer","orcid":"0000-0003-0853-2637","position":1,"is_corresponding":false},{"id":248027,"name":"Joni Vuorio","orcid":"0000-0003-2404-4545","position":2,"is_corresponding":false},{"id":248028,"name":"Julie A. Tucker","orcid":"0000-0002-6119-676X","position":3,"is_corresponding":false},{"id":248029,"name":"Hauke Winkelmann","orcid":"0000-0003-3688-6854","position":4,"is_corresponding":false},{"id":248949,"name":"Sara Löchte","orcid":null,"position":5,"is_corresponding":false},{"id":248030,"name":"Tess A. Stanly","orcid":"0000-0003-3064-0925","position":6,"is_corresponding":false},{"id":248950,"name":"Katiuska Daniela Pulgar Prieto","orcid":null,"position":7,"is_corresponding":false},{"id":248031,"name":"Chetan Poojari","orcid":"0000-0001-6575-221X","position":8,"is_corresponding":false},{"id":248032,"name":"Vivek Sharma","orcid":"0000-0002-8838-3151","position":9,"is_corresponding":false},{"id":247894,"name":"Christian Richter","orcid":"0000-0002-5420-2826","position":10,"is_corresponding":false},{"id":248033,"name":"Rainer Kurre","orcid":"0000-0002-6872-6567","position":11,"is_corresponding":false},{"id":248034,"name":"Stevan R. Hubbard","orcid":"0000-0002-2707-9383","position":12,"is_corresponding":false},{"id":218189,"name":"K. Christopher García","orcid":"0000-0001-9273-0278","position":13,"is_corresponding":false},{"id":248035,"name":"Ignacio Moraga","orcid":"0000-0001-9909-0701","position":14,"is_corresponding":false},{"id":248036,"name":"Ilpo Vattulainen","orcid":"0000-0001-7408-3214","position":15,"is_corresponding":false},{"id":248037,"name":"Ian S. Hitchcock","orcid":"0000-0001-7170-6703","position":16,"is_corresponding":false},{"id":248038,"name":"Jacob Piehler","orcid":"0000-0002-2143-2270","position":17,"is_corresponding":false},{"id":248025,"name":"Stephan Wilmes","orcid":"0000-0002-4112-710X","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T20:38:25.860949Z","pmid":"32029621","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":[]}