| http://purl.uniprot.org/citations/32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32404425 | http://www.w3.org/2000/01/rdf-schema#comment | "Endothelial cell nitric oxide (NO) synthase (eNOS), the enzyme responsible for synthesis of NO in endothelial cells, is regulated by complex posttranslational mechanisms. Sinusoidal portal hypertension, a disorder characterized by liver sinusoidal endothelial cell (SEC) injury with resultant reduced eNOS activity and NO production within the liver, has been associated with defects in eNOS protein-protein interactions and posttranslational modifications. We and others have previously identified novel eNOS interactors, including G protein-coupled receptor (GPCR) kinase interactor 1 (GIT1), which we found to play an unexpected stimulatory role in GPCR-mediated eNOS signaling. Here we report that β-arrestin 2 (β-Arr2), a canonical GPCR signaling partner, localizes in SECs with eNOS in a GIT1/eNOS/NO signaling module. Most importantly, we show that β-Arr2 stimulates eNOS activity, and that β-Arr2 expression is reduced and formation of the GIT1/eNOS/NO signaling module is interrupted during liver injury. In β-Arr2-deficient mice, bile duct ligation injury (BDL) led to significantly reduced eNOS activity and to a dramatic increase in portal hypertension compared to BDL in wild-type mice. Overexpression of β-Arr2 in injured or β-Arr2-deficient SECs rescued eNOS function by increasing eNOS complex formation and NO production. We also found that β-Arr2-mediated GIT1/eNOS complex formation is dependent on Erk1/2 and Src, two kinases known to interact with and be activated by β-Arr2 in response to GCPR activation. Our data emphasize that β-Arr2 is an integral component of the GIT1/eNOS/NO signaling pathway and have implications for the pathogenesis of sinusoidal portal hypertension."xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1922608117"xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/author | "Liu S."xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/author | "Premont R.T."xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/author | "Luttrell L.M."xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/author | "Rockey D.C."xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/pages | "11483-11492"xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/title | "beta-Arrestin2 is a critical component of the GPCR-eNOS signalosome."xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://purl.uniprot.org/core/volume | "117"xsd:string |
| http://purl.uniprot.org/citations/32404425 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32404425 |
| http://purl.uniprot.org/citations/32404425 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/32404425 |
| http://purl.uniprot.org/uniprot/#_E9Q9X4-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_E0CY53-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_E0CYB1-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_A0A158SIT9-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_J3QN53-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_F7DF62-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_G3UZ54-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_J3QNU6-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_J3QNV6-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_Q3U172-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |
| http://purl.uniprot.org/uniprot/#_J3JS97-mappedCitation-32404425 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/32404425 |