{"doi":"10.1074/jbc.m115.644773","title":"G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs)","abstract":null,"journal":"Journal of Biological Chemistry","year":2015,"id":604115,"datarank":0.6261580904843456,"base_score":4.174387269895637,"endowment":4.174387269895637,"self_citation_contribution":0.6261580904843456,"citation_network_contribution":0.0,"self_endowment_contribution":0.6261580904843456,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":64,"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":1549900,"name":"Kristoff T. Homan","orcid":null,"position":1,"is_corresponding":false},{"id":382923,"name":"Sergey A. Vishnivetskiy","orcid":"0000-0001-8619-4157","position":2,"is_corresponding":false},{"id":227709,"name":"Aashish Manglik","orcid":"0000-0002-7173-3741","position":3,"is_corresponding":false},{"id":1549901,"name":"John J.G. Tesmer","orcid":null,"position":4,"is_corresponding":false},{"id":271822,"name":"Vsevolod V. Gurevich","orcid":"0000-0002-3950-5351","position":5,"is_corresponding":false},{"id":271823,"name":"Eugenia V. Gurevich","orcid":"0000-0002-0563-8295","position":6,"is_corresponding":false},{"id":338559,"name":"Lingyong Li","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"G Protein-coupled Receptor Kinases of the GRK4 Protein Subfamily Phosphorylate Inactive G Protein-coupled Receptors (GPCRs)","abstract":"G protein-coupled receptor (GPCR) kinases (GRKs) play a key role in homologous desensitization of GPCRs. It is widely assumed that most GRKs selectively phosphorylate only active GPCRs. Here, we show that although this seems to be the case for the GRK2/3 subfamily, GRK5/6 effectively phosphorylate inactive forms of several GPCRs, including β2-adrenergic and M2 muscarinic receptors, which are commonly used as representative models for GPCRs. Agonist-independent GPCR phosphorylation cannot be explained by constitutive activity of the receptor or membrane association of the GRK, suggesting that it is an inherent ability of GRK5/6. Importantly, phosphorylation of the inactive β2-adrenergic receptor enhanced its interactions with arrestins. Arrestin-3 was able to discriminate between phosphorylation of the same receptor by GRK2 and GRK5, demonstrating preference for the latter. Arrestin recruitment to inactive phosphorylated GPCRs suggests that not only agonist activation but also the complement of GRKs in the cell regulate formation of the arrestin-receptor complex and thereby G protein-independent signaling.","is_dataset_classified":null,"base_score":4.174387269895637,"endowment":4.174387269895637,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25770216","pmcid":"PMC4409243","openalex_id":"https://openalex.org/W2049648432","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"NS065868","title":null},{"funder_name":"National Institutes of Health","grant_id":"R21DA030103","title":null},{"funder_name":"National Institutes of Health","grant_id":"GM077561","title":null},{"funder_name":"National Institutes of Health","grant_id":"EY011500","title":null},{"funder_name":"National Institutes of Health","grant_id":"HL071818","title":null},{"funder_name":"National Institutes of Health","grant_id":"HL086865","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM077561","title":null},{"funder_name":"NEI NIH HHS","grant_id":"R01 EY011500","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL071818","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM109955","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL086865","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS065868","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008294","title":null}],"total_grants":13,"fwci":3.5808,"citation_percentile":0.93644377,"influential_citations":0,"citation_trend":[{"year":2015,"count":7},{"year":2016,"count":8},{"year":2017,"count":4},{"year":2018,"count":7},{"year":2019,"count":6},{"year":2020,"count":4},{"year":2021,"count":5},{"year":2022,"count":5},{"year":2023,"count":6},{"year":2024,"count":6},{"year":2025,"count":3},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925820426092/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925820426092/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820426092?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925820426092?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.M115.644773","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.m115.644773","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25770216","host_type":"repository"},{"url":"https://escholarship.org/uc/item/2ck4q1v9","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4409243","host_type":"repository"}],"fields_of_study":["Receptor Mechanisms and Signaling","Neuropeptides and Animal Physiology","Protein Kinase Regulation and GTPase Signaling","Animals","Arrestins","Cattle","G-Protein-Coupled Receptor Kinase 4","G-Protein-Coupled Receptor Kinases","HEK293 Cells","Humans","Mutagenesis, Site-Directed","Phosphorylation","Receptors, G-Protein-Coupled","Recombinant Proteins"],"mesh_terms":["Animals","Cattle","Humans","Phosphorylation","Recombinant Proteins","Mutagenesis, Site-Directed","Arrestins","Receptors, G-Protein-Coupled","G-Protein-Coupled Receptor Kinases","G-Protein-Coupled Receptor Kinase 4","HEK293 Cells"],"keywords":["G protein-coupled receptor kinase","G protein-coupled receptor","Rhodopsin-like receptors","Arrestin","Beta adrenergic receptor kinase","Homologous desensitization","Phosphorylation","Biology","Cell biology","Receptor","Biochemistry","Agonist","Metabotropic receptor","Rhodopsin","Activation","adrenergic receptor","G Protein-coupled Receptor (Gpcr)"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T23:23:32.314847Z","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":[]}