ArticleProceedings of the National Academy of Sciences of the United States of America2020
β-Arrestin2 is a critical component of the GPCR-eNOS signalosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Tumor-Selective Vascular Modulation by Acid-Cleavable Retro-Inverso Bradykinin Conjugates Enhances the Antitumor Efficacy of Nanomedicine.ACS omega · 2026Article
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- Beta arrestin 1 is a key regulator of pulmonary vascular tone.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- S-Nitrosylation of GPCR Regulatory Machinery as a Mechanism to Bias Signaling.Handbook of experimental pharmacology · 2026Review
- β-arrestin2: an emerging player and potential therapeutic target in inflammatory immune diseases.Acta pharmacologica Sinica · 2025Review
- Advancements in Beta-Adrenergic Therapy and Novel Personalised Approach for Portal Hypertension: A Narrative Review.Life (Basel, Switzerland) · 2025Review
- Subcellular Localization Guides eNOS Function.International journal of molecular sciences · 2024Review
- β-Arrestin pathway activation by selective ATR1 agonism promotes calcium influx in podocytes, leading to glomerular damage.Clinical science (London, England : 1979) · 2023Article
- Hepatic β-arrestins: potential roles in liver health and disease.Molecular biology reports · 2023Review
- β-arrestin1 regulates astrocytic reactivity via Drp1-dependent mitochondrial fission: implications in postoperative delirium.Journal of neuroinflammation · 2023Article
- Structural Basis of the Interaction of the G Proteins, GαiBiomedicines · 2023Article
- β-PIX cooperates with GIT1 to regulate endothelial nitric oxide synthase in sinusoidal endothelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Role of Signaling Pathways in the Viral Life Cycle 2.0.International journal of molecular sciences · 2022Article
- Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?Frontiers in medicine · 2022Review
- Novel Pharmacology Following Heteromerization of the Angiotensin II Type 2 Receptor and the Bradykinin Type 2 Receptor.Frontiers in endocrinology · 2022Article
- Portal hypertension in cirrhosis: Pathophysiological mechanisms and therapy.JHEP reports : innovation in hepatology · 2021Review
- Statins for treatment of chronic liver disease.Current opinion in gastroenterology · 2021Review
- Beta-Arrestins and Receptor Signaling in the Vascular Endothelium.Biomolecules · 2020Review
- Reply to Schierwagen et al.: β-Arrestins in liver disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- β-Arrestin2 is increased in liver fibrosis in humans and rodents.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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- Erratum issued
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.