{"doi":"10.3390/ijms13055364","title":"Role of 14-3-3ζ in Platelet Glycoprotein Ibα-von Willebrand Factor Interaction-Induced Signaling","abstract":"<jats:p>The interaction of platelet glycoprotein (GP) Ib-IX with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture initiates platelet transient adhesion to the injured vessel wall, which triggers intracellular signaling cascades leading to platelet activation and thrombus formation. 14-3-3ζ has been verified to regulate the VWF binding function of GPIb-IX by interacting with the cytoplasmic domains of GPIb-IX. However, the data regarding the role of 14-3-3ζ in GPIb-IX-VWF interaction-induced signaling still remain controversial. In the present study, the data indicate that the S609A mutation replacing Ser609 of GPIbα with alanine (S609A) significantly prevented the association of 14-3-3ζ with GPIbα before and after the VWF binding to GPIbα. GPIb-IX-VWF interaction-induced activations of Src family kinases and protein kinase C were clearly reduced in S609A mutation. Furthermore, S609A mutation significantly inhibited GPIb-IX-VWF interaction-induced elevation of cytoplasmic Ca2+ levels in flow cytometry analysis. Taken together, these data indicate that the association of 14-3-3ζ with the cytoplasmic domain of GPIbα plays an important role in GPIb-IX-VWF interaction-induced signaling.</jats:p>","journal":"International Journal of Molecular Sciences","year":2012,"id":676103,"datarank":0.705197622800994,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.3598098588518871,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.3598098588518871,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":7,"citers_with_citation_signal":5,"citers_with_endowment":5,"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":1005190,"name":"Lili Zhao","orcid":"0000-0001-5735-7666","position":1,"is_corresponding":false},{"id":783560,"name":"Jun Liu","orcid":"0000-0002-8175-6293","position":2,"is_corresponding":false},{"id":408975,"name":"Juan Du","orcid":"0000-0003-3444-5043","position":3,"is_corresponding":false},{"id":1395160,"name":"Rong Yan","orcid":"0009-0009-8267-9793","position":4,"is_corresponding":false},{"id":179110,"name":"Kesheng Dai","orcid":null,"position":5,"is_corresponding":false},{"id":1520027,"name":"Weilin Zhang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of 14-3-3ζ in Platelet Glycoprotein Ibα-von Willebrand Factor Interaction-Induced Signaling","abstract":"<jats:p>The interaction of platelet glycoprotein (GP) Ib-IX with von Willebrand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture initiates platelet transient adhesion to the injured vessel wall, which triggers intracellular signaling cascades leading to platelet activation and thrombus formation. 14-3-3ζ has been verified to regulate the VWF binding function of GPIb-IX by interacting with the cytoplasmic domains of GPIb-IX. However, the data regarding the role of 14-3-3ζ in GPIb-IX-VWF interaction-induced signaling still remain controversial. In the present study, the data indicate that the S609A mutation replacing Ser609 of GPIbα with alanine (S609A) significantly prevented the association of 14-3-3ζ with GPIbα before and after the VWF binding to GPIbα. GPIb-IX-VWF interaction-induced activations of Src family kinases and protein kinase C were clearly reduced in S609A mutation. Furthermore, S609A mutation significantly inhibited GPIb-IX-VWF interaction-induced elevation of cytoplasmic Ca2+ levels in flow cytometry analysis. Taken together, these data indicate that the association of 14-3-3ζ with the cytoplasmic domain of GPIbα plays an important role in GPIb-IX-VWF interaction-induced signaling.</jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22754302","pmcid":"PMC3382782","openalex_id":"https://openalex.org/W1985773595","authors":[],"funders":[],"total_grants":0,"fwci":0.3291,"citation_percentile":0.57932429,"influential_citations":0,"citation_trend":[{"year":2013,"count":1},{"year":2015,"count":1},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2024,"count":2},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/13/5/5364/pdf?version=1403144172","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/13/5/5364/pdf?version=1403144172","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/13/5/5364/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms13055364","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22754302","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3382782","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.387.9560","host_type":""},{"url":"https://doaj.org/article/8018fb99f6a84608b706e6ee0a5c945f","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC3382782","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC3382782?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Platelet Disorders and Treatments","Peptidase Inhibition and Analysis","Cell Adhesion Molecules Research"],"mesh_terms":["Animals","Cricetulus","Humans","von Willebrand Factor","Signal Transduction","CHO Cells","Point Mutation","Platelet Glycoprotein GPIb-IX Complex","14-3-3 Proteins","Protein Interaction Maps"],"keywords":["Von Willebrand factor","Platelet membrane glycoprotein","Platelet Glycoprotein GPIb-IX Complex","Glycoprotein Ib","Platelet","Chemistry","Cell biology","Glycoprotein","Mutation","Plasma protein binding","Molecular biology","Biology","Immunology","Biochemistry","Gene","Platelets","Glycoprotein (Gp) Ib-ix","Von Willebrand Factor (Vwf)","14-3-3Ζ"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T02:06:23.885057Z","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":[]}