{"doi":"10.1126/sciadv.abq3363","title":"Control of Gα\n            <sub>q</sub>\n            signaling dynamics and GPCR cross-talk by GRKs","abstract":"<jats:p>\n            Numerous processes contribute to the regulation of G protein–coupled receptors (GPCRs), but relatively little is known about rapid mechanisms that control signaling on the seconds time scale or regulate cross-talk between receptors. Here, we reveal that the ability of some GPCR kinases (GRKs) to bind Gα\n            <jats:sub>q</jats:sub>\n            both drives acute signaling desensitization and regulates functional interactions between GPCRs. GRK2/3-mediated acute desensitization occurs within seconds, is rapidly reversible, and can occur upon local, subcellular activation. This rapid desensitization is kinase independent, insensitive to pharmacological inhibition, and generalizable across receptor families and effectors. We also find that the ability of GRK2 to bind G proteins also enables it to regulate the extent and timing of Gα\n            <jats:sub>q</jats:sub>\n            -dependent signaling cross-talk between GPCRs. Last, we find that G protein/GRK2 interactions enable a novel form of GPCR trafficking cross-talk. Together, this work reveals potent forms of Gα\n            <jats:sub>q</jats:sub>\n            -dependent GPCR regulation with wide-ranging pharmacological and physiological implications.\n          </jats:p>","journal":"Science Advances","year":2022,"id":600704,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":648571,"name":"Amanda Acosta-Ruiz","orcid":"0000-0002-7591-4128","position":1,"is_corresponding":false},{"id":848328,"name":"Arthur Radoux-Mergault","orcid":"0000-0001-7425-0350","position":2,"is_corresponding":false},{"id":1169781,"name":"Melanie Kristt","orcid":"0000-0003-4882-6162","position":3,"is_corresponding":false},{"id":1032157,"name":"Jihye Kim","orcid":"0000-0002-2525-2744","position":4,"is_corresponding":false},{"id":702009,"name":"Jared D. Moon","orcid":"0000-0002-3544-7799","position":5,"is_corresponding":false},{"id":260273,"name":"Johannes Broichhagen","orcid":"0000-0003-3084-6595","position":6,"is_corresponding":false},{"id":255551,"name":"Asuka Inoue","orcid":"0000-0003-0805-4049","position":7,"is_corresponding":false},{"id":72619,"name":"Francis S. Lee","orcid":"0000-0002-7108-9650","position":8,"is_corresponding":false},{"id":351505,"name":"Miriam Stoeber","orcid":"0000-0002-5210-2864","position":9,"is_corresponding":false},{"id":550486,"name":"Jeremy S. Dittman","orcid":"0000-0002-3850-9078","position":10,"is_corresponding":false},{"id":577472,"name":"Joshua Levitz","orcid":"0000-0002-8169-6323","position":11,"is_corresponding":false},{"id":703823,"name":"Guoqing Xiang","orcid":"0000-0003-1111-9675","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Control of Gα\n            <sub>q</sub>\n            signaling dynamics and GPCR cross-talk by GRKs","abstract":"<jats:p>\n            Numerous processes contribute to the regulation of G protein–coupled receptors (GPCRs), but relatively little is known about rapid mechanisms that control signaling on the seconds time scale or regulate cross-talk between receptors. Here, we reveal that the ability of some GPCR kinases (GRKs) to bind Gα\n            <jats:sub>q</jats:sub>\n            both drives acute signaling desensitization and regulates functional interactions between GPCRs. GRK2/3-mediated acute desensitization occurs within seconds, is rapidly reversible, and can occur upon local, subcellular activation. This rapid desensitization is kinase independent, insensitive to pharmacological inhibition, and generalizable across receptor families and effectors. We also find that the ability of GRK2 to bind G proteins also enables it to regulate the extent and timing of Gα\n            <jats:sub>q</jats:sub>\n            -dependent signaling cross-talk between GPCRs. Last, we find that G protein/GRK2 interactions enable a novel form of GPCR trafficking cross-talk. Together, this work reveals potent forms of Gα\n            <jats:sub>q</jats:sub>\n            -dependent GPCR regulation with wide-ranging pharmacological and physiological implications.\n          </jats:p>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36427324","pmcid":"PMC9699688","openalex_id":"https://openalex.org/W4309958306","authors":[],"funders":[{"funder_name":"NIDA NIH HHS","grant_id":"R01 DA054368","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"181282","title":"Mechanisms Underlying Subcellular Location Bias of Opioid Receptor Signaling"},{"funder_name":"NIMH NIH HHS","grant_id":"R01 MH118451","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS116747","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R35 GM124731","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"120218","title":"Self-Interacting Random Processes, Stochastic Approximations.&amp;Dimer, Ising and Polymer Models in Statistical Mechanics."},{"funder_name":"National Institutes of Health","grant_id":"5R35GM124731-02","title":"Molecular Mechanisms of Synaptic G Protein-Coupled Receptors"},{"funder_name":"National Institutes of Health","grant_id":"1F32GM013039-01","title":"MOLECULAR ANALYSIS OF THE YEAST HEAT SHOCK TRANSCRIPTION"},{"funder_name":"National Institutes of Health","grant_id":"5R01NS116747-13","title":"Analysis of Synaptic Protein Dynamics"}],"total_grants":9,"fwci":1.5949,"citation_percentile":0.83615298,"influential_citations":0,"citation_trend":[{"year":2023,"count":9},{"year":2024,"count":7},{"year":2025,"count":3},{"year":2026,"count":4}],"oa_status":"gold","license":"http://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.","oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.abq3363?download=true","host_type":"journal"},{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.abq3363?download=true","host_type":"publisher"},{"url":"https://www.science.org/doi/pdf/10.1126/sciadv.abq3363","host_type":"publisher"},{"url":"https://doi.org/10.1126/sciadv.abq3363","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36427324","host_type":"repository"},{"url":"https://archive-ouverte.unige.ch/unige:165354","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9699688","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9699688","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9699688?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1126/sciadv.abq3363","host_type":""}],"fields_of_study":["Receptor Mechanisms and Signaling","Protein Kinase Regulation and GTPase Signaling","Neuropeptides and Animal Physiology","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["G protein-coupled receptor","G protein-coupled receptor kinase","Beta adrenergic receptor kinase","Desensitization (medicine)","Effector","Receptor","Cell biology","Biology","Signal transduction","G protein","Kinase","Computational biology","Biochemistry","612","Biomedicine and Life Sciences"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"pdb"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T13:54:50.037119Z","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":[]}