ArticleThe Biochemical journal2001
Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells.
Article in The Biochemical journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 179 citations in OpenAlex.
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- Vascular endothelial cell morphology and alignment regulate VEGF-induced endothelial nitric oxide synthase activation.Cytoskeleton (Hoboken, N.J.) · 2024Article
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- ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning.Development (Cambridge, England) · 2022Article
- N-VEGF, the Autoregulatory Arm of VEGF-A.Cells · 2022Article
- Beta-arrestins operate an on/off control switch for focal adhesion kinase activity.Cellular and molecular life sciences : CMLS · 2020Article
- CD146, from a melanoma cell adhesion molecule to a signaling receptor.Signal transduction and targeted therapy · 2020Review
- Raftlin is recruited by neuropilin-1 to the activated VEGFR2 complex to control proangiogenic signaling.Angiogenesis · 2020Article
- Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells.International journal of molecular sciences · 2020Article
- Target Elimination-Denatured and Unstable Proteins, Environmental Toxins, Metabolic Wastes, Immunosuppressive Factors and Chronic Inflammatory Factors of Medical System for Chronic Diseases Prevention and Health Promotion: A Narrative Review.Iranian journal of public health · 2019Review
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- Molecular Pharmacology of VEGF-A Isoforms: Binding and Signalling at VEGFR2.International journal of molecular sciences · 2018Review
- Ethanol Enhances Estrogen Mediated Angiogenesis in Breast Cancer.Journal of Cancer · 2018Article
- Vascular Endothelial Growth Factor (VEGF) Promotes Assembly of the p130Cas Interactome to Drive Endothelial Chemotactic Signaling and Angiogenesis.Molecular & cellular proteomics : MCP · 2017Article
- Antiangiogenic effect of dasatinib in murine models of oxygen-induced retinopathy and laser-induced choroidal neovascularization.Molecular vision · 2017Article
- Regulation of pulmonary endothelial barrier function by kinases.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- LRRK2 Inhibits FAK Activity by Promoting FERM-mediated Autoinhibition of FAK and Recruiting the Tyrosine Phosphatase, SHP-2.Experimental neurobiology · 2016Article
- Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway.Oncotarget · 2016Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial growth factor (VEGF) stimulates the tyrosine phosphorylation of focal adhesion kinase (FAK), increases focal adhesion formation and is chemotactic for human umbilical-vein endothelial cells (HUVECs). In the present study we identified the major sites of VEGF-induced FAK tyrosine phosphorylation and investigated the mechanism mediating this pathway in the action of VEGF. VEGF increased the focal adhesion localization of FAK phosphorylated at Tyr-397 (Y397) and Y861 but stimulated a marked increase in phosphorylation at Y861 without significantly affecting the total level of phospho-Y397 FAK. Inhibition of Src with the specific inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) completely blocked VEGF-induced Y861 phosphorylation without decreasing the level of phospho-Y397 FAK. We also examined the role of Src in mediating endothelial functions of VEGF in which FAK has been implicated as having a role. PP2 markedly inhibited VEGF-induced chemotaxis and wound-healing cell migration. The Src inhibitor also decreased the anti-apoptotic effect of VEGF determined by surface staining of annexin V but did not increase FAK proteolysis or prevent the VEGF-dependent inhibition of FAK proteolysis. In contrast, the specific PtdIns 3-kinase inhibitor LY294002 induced apoptosis and markedly decreased p125(FAK) expression and increased FAK proteolysis but had little effect on Y861 phosphorylation. These findings identify Src-dependent FAK phosphorylation at Y861 as a novel VEGF-induced signalling pathway in endothelial cells and suggest that this pathway might be involved in the mechanisms mediating VEGF-induced endothelial cell migration and anti-apoptosis.
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