ArticleCellular signalling2016
PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026Review
- Effects of Mechanical Stress on Endothelial Cells In Situ and In Vitro.International journal of molecular sciences · 2023Review
- CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer's disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.American journal of physiology. Cell physiology · 2023Review
- Small RNA Sequencing Revealed that miR4415, a Legume-Specific miRNA, was Involved in the Cold Acclimation ofFrontiers in genetics · 2022Article
- Protein kinase N2 mediates flow-induced endothelial NOS activation and vascular tone regulation.The Journal of clinical investigation · 2021Article
- Heparan sulfate proteoglycan glypican-1 and PECAM-1 cooperate in shear-induced endothelial nitric oxide production.Scientific reports · 2021Article
- The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.Cardiovascular engineering and technology · 2021Review
- Mechanobiology of Microvascular Function and Structure in Health and Disease: Focus on the Coronary Circulation.Frontiers in physiology · 2021Review
- Where the Action Is-Leukocyte Recruitment in Atherosclerosis.Frontiers in cardiovascular medicine · 2021Review
- Enhanced Autophagy in GAB1-Deficient Vascular Endothelial Cells Is Responsible for Atherosclerosis Progression.Frontiers in physiology · 2020Article
- Heparin-Binding Protein: A Novel Biomarker Linking Four Different Cardiovascular Diseases.Cardiology research and practice · 2020Article
- Pivotal micro factors associated with endothelial cells.Chinese medical journal · 2019Review
- Improved detection of common variants in coronary artery disease and blood pressure using a pleiotropy cFDR method.Scientific reports · 2019Article
- Roles of eNOS in atherosclerosis treatment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Review
- T Cell Receptor-Independent, CD31/IL-17A-Driven Inflammatory Axis Shapes Synovitis in Juvenile Idiopathic Arthritis.Frontiers in immunology · 2018Article
- Flow-dependent epigenetic regulation of IGFBP5 expression by H3K27me3 contributes to endothelial anti-inflammatory effects.Theranostics · 2018Article
- Atheroprotective laminar flow inhibits Hippo pathway effector YAP in endothelial cells.Translational research : the journal of laboratory and clinical medicine · 2016Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial dysfunction, characterized by impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued decrease of NO production, is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Laminar blood flow-mediated specific signaling cascades modulate vascular endothelial cells (ECs) structure and functions. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation in ECs, which in part confers laminar flow atheroprotective action. However, the molecular mechanisms whereby flow regulates Gab1 tyrosine phosphorylation and its downstream signaling events remain unclear. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in flow signaling and HGF signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K decreased flow-, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs.
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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 OpenQuestion graph.