ArticleCell death & disease2019
β-arrestin-2 in PAR-1-biased signaling has a crucial role in endothelial function via PDGF-β in stroke.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026Review
- In vivo neuroprotection in ischemic stroke by activated protein C requires β-arrestin 2.Blood vessels, thrombosis & hemostasis · 2025Article
- Characterizing Modulators of Protease-activated Receptors with a Calcium Mobilization Assay Using a Plate Reader.Journal of visualized experiments : JoVE · 2024Article
- Autoantibodies Targeting G-Protein-Coupled Receptors: Pathogenetic, Clinical and Therapeutic Implications in Systemic Sclerosis.International journal of molecular sciences · 2024Review
- The ATMolecules (Basel, Switzerland) · 2023Review
- Endothelial APC/PAR1 distinctly regulates cytokine-induced pro-inflammatory VCAM-1 expression.Frontiers in molecular biosciences · 2023Article
- MiRNA-132/212 regulates tight junction stabilization in blood-brain barrier after stroke.Cell death discovery · 2021Article
- aPC/PAR1 confers endothelial anti-apoptotic activity via a discrete, β-arrestin-2-mediated SphK1-S1PR1-Akt signaling axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Targeting the Angiotensin II Type 1 Receptor in Cerebrovascular Diseases: Biased Signaling Raises New Hopes.International journal of molecular sciences · 2021Review
- Beta-Arrestins and Receptor Signaling in the Vascular Endothelium.Biomolecules · 2020Review
- CREB Coactivator CRTC2 Plays a Crucial Role in Endothelial Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Phosphoproteomic analysis of protease-activated receptor-1 biased signaling reveals unique modulators of endothelial barrier function.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombin aggravates ischemic stroke and activated protein C (APC) has a neuroprotective effect. Both proteases interact with protease-activated receptor 1, which exhibits functional selectivity and leads to G-protein- and β-arrestin-mediated-biased signal transduction. We focused on the effect of β-arrestin in PAR-1-biased signaling on endothelial function after stroke or high-fat diet (HFD). Thrombin had a rapid disruptive effect on endothelial function, but APC had a slow protective effect. Paralleled by prolonged MAPK 42/44 signaling activation by APC via β-arrestin-2, a lower cleavage rate of PAR-1 for APC than thrombin was quantitatively visualized by bioluminescence video imaging. HFD-fed mice showed lower β-arrestin-2 levels and more severe ischemic injury. The expression of β-arrestin-2 in capillaries and PDGF-β secretion in HFD-fed mice were reduced in penumbra lesions. These results suggested that β-arrestin-2-MAPK-PDGF-β signaling enhanced protection of endothelial function and barrier integrity after stroke.
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