ArticleCirculation research2008
Localized alpha4 integrin phosphorylation directs shear stress-induced endothelial cell alignment.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 53 citations in OpenAlex.
- Integrin α4 and α9 in trabecular meshwork and Schlemm's canal function: emerging regulators of intraocular pressure homeostasis.Frontiers in cell and developmental biology · 2026Review
- Matrix stiffness, endothelial dysfunction and atherosclerosis.Molecular biology reports · 2023Review
- Vascular and Liver Homeostasis in Juvenile Mice Require Endothelial Cyclic AMP-Dependent Protein Kinase A.International journal of molecular sciences · 2022Article
- Review
- Integrin Crosstalk and Its Effect on the Biological Functions of the Trabecular Meshwork/Schlemm's Canal.Frontiers in cell and developmental biology · 2022Review
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- Syndecans and Their Synstatins: Targeting an Organizer of Receptor Tyrosine Kinase Signaling at the Cell-Matrix Interface.Frontiers in oncology · 2021Review
- Proteomics Reveals the Potential Protective Mechanism of Hydrogen Sulfide on Retinal Ganglion Cells in an Ischemia/Reperfusion Injury Animal Model.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis.Molecular biology of the cell · 2020Article
- VLA-4 phosphorylation during tumor and immune cell migration relies on its coupling to VEGFR2 and CXCR4 by syndecan-1.Journal of cell science · 2019Article
- A Membrane-Bound Biosensor Visualizes Shear Stress-Induced Inhomogeneous Alteration of Cell Membrane Tension.iScience · 2018Article
- Mechanobiological Feedback in Pulmonary Vascular Disease.Frontiers in physiology · 2018Review
- Flow-induced endothelial cell alignment requires the RhoGEF Trio as a scaffold protein to polarize active Rac1 distribution.Molecular biology of the cell · 2017Article
- Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes.Diabetes · 2016Article
- cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner.Development (Cambridge, England) · 2016Article
- Heparanase-induced shedding of syndecan-1/CD138 in myeloma and endothelial cells activates VEGFR2 and an invasive phenotype: prevention by novel synstatins.Oncogenesis · 2016Article
- Fine-tuning Tumor Immunity with Integrin Trans-regulation.Cancer immunology research · 2015Article
- Transforming growth factor β2 promotes transcription of COX2 and EP4, leading to a prostaglandin E2-driven autostimulatory loop that enhances virulence of Theileria annulata-transformed macrophages.Infection and immunity · 2015Article
- Mechanotransduction in the endothelium: role of membrane proteins and reactive oxygen species in sensing, transduction, and transmission of the signal with altered blood flow.Antioxidants & redox signaling · 2014Review
- Rac[e] to the pole: setting up polarity in endothelial cells.Small GTPases · 2014Review
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial cells respond to laminar shear stress by aligning in the direction of flow, a process which may contribute to atheroprotection. Here we report that localized alpha4 integrin phosphorylation is a mechanism for establishing the directionality of shear stress-induced alignment in microvascular endothelial cells. Within 5 minutes of exposure to a physiological level of shear stress, endothelial alpha4 integrins became phosphorylated on Ser(988). In wounded monolayers, phosphorylation was enhanced at the downstream edges of cells relative to the source of flow. The shear-induced alpha4 integrin phosphorylation was blocked by inhibitors of cAMP-dependent protein kinase A (PKA), an enzyme involved in the alignment of endothelial cells under prolonged shear. Moreover, shear-induced localized activation of the small GTPase Rac1, which specifies the directionality of endothelial alignment, was similarly blocked by PKA inhibitors. Furthermore, endothelial cells bearing a nonphosphorylatable alpha4(S(988)A) mutation failed to align in response to shear stress, thus establishing alpha4 as a relevant PKA substrate. We thereby show that shear-induced PKA-dependent alpha4 integrin phosphorylation at the downstream edge of endothelial cells promotes localized Rac1 activation, which in turn directs cytoskeletal alignment in response to shear stress.
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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 OpenQuestion graph.