ArticleThe Journal of experimental medicine2012
VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 234 citations in OpenAlex.
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- Shock Induced Endotheliopathy and High Trauma Mortality-Fight-or-Flight Response Revisited.International journal of molecular sciences · 2026Review
- GM-CSF Promotes Neutrophil PD-L1 Expression Through the VEGFR-2/STAT6/CSF2 Signaling Axis in Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nintedanib-Associated Generalized Body Swelling in a Patient With Idiopathic Pulmonary Fibrosis: A Case Report.Cureus · 2026Article
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- Vascular Endothelial Growth Factor-D Improves Lung Vascular Integrity During Acute Lung Injury.Circulation research · 2026Article
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- SHP2 regulates VEGFR2 Y1175/PLCγ signaling to impair tumor endothelial barrier stability.iScience · 2026Article
- Research progress on high-altitude hypoxia pulmonary injury: pathogenesis and Chinese herbal medicine for prevention and treatment.Frontiers in pharmacology · 2026Review
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Machine Learning-Based Prognostic Signature in Breast Cancer: Regulatory T Cells, Stemness, and Deep Learning for Synergistic Drug Discovery.International journal of molecular sciences · 2025Article
- PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases.Nature communications · 2025Article
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance.Archives of pharmacal research · 2025Review
- The Impact of Cannabidiol (CBD) on Lipid Absorption and Lymphatic Transport in Rats.Nutrients · 2025Article
- Endothelial transcriptomic, epigenomic and proteomic data challenge the proposed role for TSAd in vascular permeability.Angiogenesis · 2025Article
- PCDH17 induces colorectal cancer metastasis by destroying the vascular endothelial barrier.Cell death & disease · 2025Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Regulation of vascular endothelial (VE) growth factor (VEGF)-induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation of VEGF receptor 2 (VEGFR2) at Y951 facilitates binding of VEGFR2 to the Rous sarcoma (Src) homology 2-domain of T cell-specific adaptor (TSAd), which in turn regulates VEGF-induced activation of the c-Src tyrosine kinase and vascular permeability. c-Src was activated in vivo and in vitro in a VEGF/TSAd-dependent manner, and was regulated via increased phosphorylation at pY418 and reduced phosphorylation at pY527. Tsad silencing blocked VEGF-induced c-Src activation, but did not affect pathways involving phospholipase Cγ, extracellular regulated kinase, and endothelial nitric oxide. VEGF-induced rearrangement of VE-cadherin-positive junctions in endothelial cells isolated from mouse lungs, or in mouse cremaster vessels, was dependent on TSAd expression, and TSAd formed a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. Vessels in tsad(-/-) mice showed undisturbed flow and pressure, but impaired VEGF-induced permeability, as measured by extravasation of Evans blue, dextran, and microspheres in the skin and the trachea. Histamine-induced extravasation was not affected by TSAd deficiency. We conclude that TSAd is required for VEGF-induced, c-Src-mediated regulation of endothelial cell junctions and for vascular permeability.
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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.