{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Molinar-Inglis O"],"funding":["NICHD NIH HHS","Foundation for the National Institutes of Health","NHLBI NIH HHS","NIGMS NIH HHS"],"pagination":["e2106623118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8670512"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(49)"],"pubmed_abstract":["Endothelial dysfunction is associated with vascular disease and results in disruption of endothelial barrier function and increased sensitivity to apoptosis. Currently, there are limited treatments for improving endothelial dysfunction. Activated protein C (aPC), a promising therapeutic, signals via protease-activated receptor-1 (PAR1) and mediates several cytoprotective responses, including endothelial barrier stabilization and anti-apoptotic responses. We showed that aPC-activated PAR1 signals preferentially via β-arrestin-2 (β-arr2) and dishevelled-2 (Dvl2) scaffolds rather than G proteins to promote Rac1 activation and barrier protection. However, the signaling pathways utilized by aPC/PAR1 to mediate anti-apoptotic activities are not known. aPC/PAR1 cytoprotective responses also requi"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis."],"pmcid":["PMC8670512"],"funding_grant_id":["R01 GM116597","HL007444","P50HD12303","R00 HD098330","P50 HD012303","K12 GM068524","T32 HL007444","R25 GM083275","R35GM127121","K12GM068524","R25GM083275","R35 GM127121"],"pubmed_authors":["Orduna-Castillo L","Molinar-Inglis O","Trejo J","Coronel LJ","Birch CA","Nicholas D","Chen B","Lawson MA","Patwardhan A","Cisneros-Aguirre M","Gomez Menzies PK","Lin H","Grimsey NJ","Patel HH"],"additional_accession":[]},"is_claimable":false,"name":"aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis.","description":"Endothelial dysfunction is associated with vascular disease and results in disruption of endothelial barrier function and increased sensitivity to apoptosis. Currently, there are limited treatments for improving endothelial dysfunction. Activated protein C (aPC), a promising therapeutic, signals via protease-activated receptor-1 (PAR1) and mediates several cytoprotective responses, including endothelial barrier stabilization and anti-apoptotic responses. We showed that aPC-activated PAR1 signals preferentially via β-arrestin-2 (β-arr2) and dishevelled-2 (Dvl2) scaffolds rather than G proteins to promote Rac1 activation and barrier protection. However, the signaling pathways utilized by aPC/PAR1 to mediate anti-apoptotic activities are not known. aPC/PAR1 cytoprotective responses also requi","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Dec","modification":"2025-04-04T07:47:55.12Z","creation":"2025-04-04T07:47:55.12Z"},"accession":"S-EPMC8670512","cross_references":{"pubmed":["34873055"],"doi":["10.1073/pnas.2106623118"]}}