ArticleThe Journal of biological chemistry2013
Tetraspanin CD63 promotes vascular endothelial growth factor receptor 2-β1 integrin complex formation, thereby regulating activation and downstream signaling in endothelial cells in vitro and in vivo.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- Antagonistic SMAD2/3 control of TIMP-1, VEGF-A, and hypoxia signaling in myofibroblasts shapes histotype-specific angiogenesis in lung cancer.Cell death & disease · 2026Article
- Thioredoxin and tetraspanin 30 (CD63) as potential biomarkers for angioinvasion in papillary thyroid cancer.Scientific reports · 2025Article
- Pro-Angiogenic Bioactive Molecules in Vascular Morphogenesis: Integrating Endothelial Cell Dynamics.Current issues in molecular biology · 2025Review
- Systematic correlation analysis of human CD molecules reveals upregulated co-expression of CD58, CD63, and CD147 in patients with primary Sjögren's syndrome.Immunologic research · 2025Article
- Tetraspanin CD82 regulates transforming growth factor-β signaling in hematopoietic stem and progenitor cells.Molecular biology of the cell · 2025Article
- Endothelial TDP-43 depletion disrupts core blood-brain barrier pathways in neurodegeneration.Nature neuroscience · 2025Article
- Mapping Organism-wide Single Cell mRNA Expression Linked to Extracellular Vesicle Biogenesis, Secretion, and Cargo.Function (Oxford, England) · 2025Article
- Tetraspanin-enriched microdomains play an important role in pathogenesis in the protozoan parasite Entamoeba histolytica.PLoS pathogens · 2024Article
- The identification of a Distinct Astrocyte Subtype that Diminishes in Alzheimer's Disease.Aging and disease · 2024Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- CD11c+ macrophages are proangiogenic and necessary for experimental choroidal neovascularization.JCI insight · 2023Article
- Developmental diversity and unique sensitivity to injury of lung endothelial subtypes during postnatal growth.iScience · 2023Article
- Stabilized COre gene and Pathway Election uncovers pan-cancer shared pathways and a cancer-specific driver.Science advances · 2022Article
- Broussonin A- and B-mediated inhibition of angiogenesis by blockade of VEGFR-2 signalling pathways and integrin β1 expression.Journal of cellular and molecular medicine · 2022Article
- Hemocyte response to treatment of susceptible and resistant Asian corn borer (Frontiers in immunology · 2022Article
- Characteristics of TIMP1, CD63, and β1-Integrin and the Functional Impact of Their Interaction in Cancer.International journal of molecular sciences · 2021Review
- Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia.Thrombosis and haemostasis · 2021Article
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- Changes in protein expression due to metformin treatment and hyperinsulinemia in a human endometrial cancer cell line.PloS one · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD63 is a member of the transmembrane-4 glycoprotein superfamily (tetraspanins) implicated in the regulation of membrane protein trafficking, leukocyte recruitment, and adhesion processes. We have investigated the involvement of CD63 in endothelial cell (EC) signaling downstream of β1 integrin and VEGF. We report that silencing of CD63 in primary ECs arrested capillary sprouting and tube formation in vitro because of impaired adhesion and migration of ECs. Mechanistically, CD63 associated with both β1 integrin and the main VEGF receptor on ECs, VEGFR2. Our data suggest that CD63 serves to bridge between β1 integrin and VEGFR2 because CD63 silencing disrupted VEGFR2-β1 integrin complex formation identified using proximity ligation assays. Signaling downstream of β1 integrin and VEGFR2 was attenuated in CD63-silenced cells, although their cell surface expression levels remained unaffected. CD63 was furthermore required for efficient internalization of VEGFR2 in response to VEGF. Importantly, systemic delivery of VEGF failed to potently induce VEGFR2 phosphorylation and downstream signaling in CD63-deficient mouse lungs. Taken together, our findings demonstrate a previously unrecognized role for CD63 in coordinated integrin and receptor tyrosine kinase signaling in vitro and in vivo.
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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.