{"doi":"10.1101/629576","title":"Noncanonical scaffolding of G\n                  <sub>αi</sub>\n                  and β-arrestin by G protein-coupled receptors","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  G-protein-coupled receptors (GPCRs) enable cells to sense and respond appropriately to hormonal and environmental signals, and are a target of ~30% of all FDA-approved medications. Canonically, each GPCR couples to distinct G\n                  <jats:sub>α</jats:sub>\n                  proteins, such as G\n                  <jats:sub>αs</jats:sub>\n                  , G\n                  <jats:sub>αi</jats:sub>\n                  , G\n                  <jats:sub>αq</jats:sub>\n                  or G\n                  <jats:sub>α12/13</jats:sub>\n                  , as well as β-arrestins. These transducer proteins translate and integrate extracellular stimuli sensed by GPCRs into intracellular signals through what are broadly considered separable signalling pathways. However, the ability of G\n                  <jats:sub>α</jats:sub>\n                  proteins to directly interact with β-arrestins to integrate signalling has not previously been appreciated. Here we show a novel interaction between G\n                  <jats:sub>αi</jats:sub>\n                  protein family members and β-arrestin. G\n                  <jats:sub>αi</jats:sub>\n                  :β-arrestin complexes were formed by all GPCRs tested, regardless of their canonical G protein isoform coupling, and could bind both GPCRs as well as the extracellular signal-regulated kinase (ERK). This novel paradigm of G\n                  <jats:sub>αi</jats:sub>\n                  :β-arrestin scaffolds enhances our understanding of GPCR signalling.\n                </jats:p>","journal":null,"year":null,"id":591981,"datarank":0.36353433220796216,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.12211864534284708,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.12211864534284708,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"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":976734,"name":"Thomas F. Pack","orcid":"0000-0002-1240-8324","position":1,"is_corresponding":false},{"id":255551,"name":"Asuka Inoue","orcid":"0000-0003-0805-4049","position":2,"is_corresponding":false},{"id":655119,"name":"Claudia Lee","orcid":"0000-0003-1715-2265","position":3,"is_corresponding":false},{"id":439415,"name":"Xinyu Xiong","orcid":"0000-0002-9803-8503","position":4,"is_corresponding":false},{"id":1154525,"name":"Kevin Zheng","orcid":"0000-0003-4654-1809","position":5,"is_corresponding":false},{"id":592095,"name":"Alem W. Kahsai","orcid":"0000-0001-9272-4484","position":6,"is_corresponding":false},{"id":717750,"name":"Issac Choi","orcid":"0000-0001-7429-8418","position":7,"is_corresponding":false},{"id":91333,"name":"Zhiyuan Ma","orcid":"0000-0003-3270-6844","position":8,"is_corresponding":false},{"id":1130899,"name":"Ian M. Levitan","orcid":"0009-0004-3147-3967","position":9,"is_corresponding":false},{"id":258561,"name":"Lauren K. Rochelle","orcid":"0000-0002-0669-1362","position":10,"is_corresponding":false},{"id":243477,"name":"Dean P. Staus","orcid":null,"position":11,"is_corresponding":false},{"id":976738,"name":"Joshua C. Snyder","orcid":"0000-0002-9787-3371","position":12,"is_corresponding":false},{"id":199917,"name":"Marc G. Caron","orcid":null,"position":13,"is_corresponding":false},{"id":354436,"name":"Sudarshan Rajagopal","orcid":"0000-0002-3443-5040","position":14,"is_corresponding":false},{"id":732425,"name":"Jeffrey S. Smith","orcid":"0000-0003-2840-2899","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Noncanonical scaffolding of G\n                  <sub>αi</sub>\n                  and β-arrestin by G protein-coupled receptors","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  G-protein-coupled receptors (GPCRs) enable cells to sense and respond appropriately to hormonal and environmental signals, and are a target of ~30% of all FDA-approved medications. Canonically, each GPCR couples to distinct G\n                  <jats:sub>α</jats:sub>\n                  proteins, such as G\n                  <jats:sub>αs</jats:sub>\n                  , G\n                  <jats:sub>αi</jats:sub>\n                  , G\n                  <jats:sub>αq</jats:sub>\n                  or G\n                  <jats:sub>α12/13</jats:sub>\n                  , as well as β-arrestins. These transducer proteins translate and integrate extracellular stimuli sensed by GPCRs into intracellular signals through what are broadly considered separable signalling pathways. However, the ability of G\n                  <jats:sub>α</jats:sub>\n                  proteins to directly interact with β-arrestins to integrate signalling has not previously been appreciated. Here we show a novel interaction between G\n                  <jats:sub>αi</jats:sub>\n                  protein family members and β-arrestin. G\n                  <jats:sub>αi</jats:sub>\n                  :β-arrestin complexes were formed by all GPCRs tested, regardless of their canonical G protein isoform coupling, and could bind both GPCRs as well as the extracellular signal-regulated kinase (ERK). This novel paradigm of G\n                  <jats:sub>αi</jats:sub>\n                  :β-arrestin scaffolds enhances our understanding of GPCR signalling.\n                </jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20725694","pmcid":null,"openalex_id":"https://openalex.org/W2944668486","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"1K08HL114643-01A1","title":"Noncanonical Receptor Signaling in Pulmonary Arterial Hypertension"},{"funder_name":"National Institutes of Health","grant_id":"5F31DA041160-02","title":"Dissecting the Distinct Arrestin Signaling Capabilities of the Short and Long Dopamine D2 Receptors as a Paradigm for Psychostimulant Addiction Treatment"},{"funder_name":"National Institutes of Health","grant_id":"1R01GM122798-01A1","title":"Biasing CXCR3 Signaling to Modulate the Inflammatory Response"}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2020,"count":4}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/07/629576.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2019/05/07/629576.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/629576","host_type":"publisher"},{"url":"https://doi.org/10.1101/629576","host_type":"repository"},{"url":"https://dx.doi.org/10.1101/629576","host_type":""},{"url":"http://dx.doi.org/10.1101/629576","host_type":""}],"fields_of_study":["Receptor Mechanisms and Signaling","Neuropeptides and Animal Physiology","Mass Spectrometry Techniques and Applications","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["G protein-coupled receptor","Arrestin","G protein","Gq alpha subunit","Cell biology","Extracellular","Signalling","G protein-coupled receptor kinase","Receptor","Scaffold protein","Signal transduction","Gene isoform","Biology","Intracellular","Chemistry","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-26T11:39:47.622413Z","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":[]}