{"doi":"10.1016/j.rpth.2024.102556","title":"G protein–coupled receptor kinase 5 regulates thrombin signaling in platelets","abstract":"Background: Our prior genome-wide association study of thrombin-induced platelet aggregation identified a G protein-coupled receptor kinase 5 (GRK5) noncoding variant (rs10886430-G) that is strongly associated with increased platelet reactivity to thrombin. This variant predisposes to increased risk of stroke, pulmonary embolism, and venous thromboembolism. Objectives: To determine role of platelet specific GRK5 in platelet responses to agonists and injury. Methods: Platelets from GRK5 mutant mice have been shown to have increased thrombin sensitivity, indicating that GRK5 may be a negative regulator of platelet activation. However, this has not been studied in a platelet-specific manner. We therefore used platelet-specific GRK5 mutant mice and models of thrombosis and pulmonary embolism. Results: . In addition, platelet GRK5 mutant mice had increased thrombin but not collagen-induced thrombus burden in a mouse model of pulmonary embolism. Conclusion: These data indicate that platelet GRK5 has a significant role in limiting platelet responses to thrombin.","journal":"Research and Practice in Thrombosis and Haemostasis","year":2024,"id":445353,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9626,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":566602,"name":"Michael W. Malloy","orcid":null,"position":1,"is_corresponding":false},{"id":251400,"name":"Sara Ture","orcid":"0000-0003-0568-8791","position":2,"is_corresponding":false},{"id":1134260,"name":"Benjamín Nieves-López","orcid":"0000-0001-9184-1398","position":3,"is_corresponding":false},{"id":356089,"name":"Florian Thibord","orcid":"0000-0003-2229-8322","position":4,"is_corresponding":false},{"id":24979,"name":"Andrew D. Johnson","orcid":"0000-0001-6369-5178","position":5,"is_corresponding":false},{"id":251415,"name":"Craig N. Morrell","orcid":"0000-0001-9131-4862","position":6,"is_corresponding":false},{"id":1167123,"name":"Chen Li","orcid":"0000-0002-4391-5898","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:01:42.089235Z","pmid":"39309233","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":[]}