ArticleThe EMBO journal2001
A single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 312 papers, 1 of them a synthesis that pooled it.
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Who cites it
312 citing papers in PubMed, 1 synthesis or guideline pooled it, 745 citations in OpenAlex.
- Does Diabetes Induce the Vascular Endothelial Growth Factor (VEGF) Expression in Periodontal Tissues? A Systematic Review.International journal of environmental research and public health · 2020Pooled it
- Apatinib Mesylate in the treatment of advanced progressed lung adenocarcinoma patients with EGFR-TKI resistance -A Multicenter Randomized Trial.Scientific reports · 2019Trial
- PINCH proteins orchestrate vascular mural cell homeostasis through integrated signaling and transcriptional networks.Angiogenesis · 2026Article
- ATP-citrate lyase is a critical regulator of physiological and pathological angiogenesis.Angiogenesis · 2026Article
- Endothelial LRRC8A mitigates pressure overload-induced cardiac hypertrophy by promoting coronary angiogenesis.Angiogenesis · 2025Article
- Cable Cars to the Nucleus: TM4SF1-Enriched Microdomains Conduct Signaling in Endothelial Cells for Blood Vessel Formation.International journal of molecular sciences · 2025Article
- Polysialic acid regulates glomerular microvasculature formation by interaction with VEGF-A188 in mice.Angiogenesis · 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
- Contribution of tumor microenvironment (TME) to tumor apoptosis, angiogenesis, metastasis, and drug resistance.Medical oncology (Northwood, London, England) · 2025Review
- Vascular Endothelial Growth Factor Receptors in the Vascularization of Pancreatic Tumors: Implications for Prognosis and Therapy.Current issues in molecular biology · 2025Review
- Translationally Controlled Tumor Protein Enhances Angiogenesis in Ovarian Tumors by Activating Vascular Endothelial Growth Factor Receptor 2 Signaling.Biomolecules & therapeutics · 2025Article
- Active peptides of TSP-1 inhibit retinal angiogenesis through the CD36 pathway in a rat model of choroidal neovascularization.PloS one · 2025Article
- Muscone abrogates breast cancer progression through tumor angiogenic suppression via VEGF/PI3K/Akt/MAPK signaling pathways.Cancer cell international · 2024Article
- TM4SF1 is a molecular facilitator that distributes cargo proteins intracellularly in endothelial cells in support of blood vessel formation.Journal of cell communication and signaling · 2024Article
- sFlt-1 impairs neurite growth and neuronal differentiation in SH-SY5Y cells and human neurons.Bioscience reports · 2024Article
- Eph-ephrin signaling couples endothelial cell sorting and arterial specification.Nature communications · 2024Article
- Tissue-resident macrophages specifically express Lactotransferrin and Vegfc during ear pinna regeneration in spiny mice.Developmental cell · 2024Article
- Molecular basis of VEGFR1 autoinhibition at the plasma membrane.Nature communications · 2024Article
- Acrizanib as a Novel Therapeutic Agent for Fundus Neovascularization via Inhibitory Phosphorylation of VEGFR2.Translational vision science & technology · 2024Article
252 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KDR/Flk-1 tyrosine kinase, one of the two vascular endothelial growth factor (VEGF) receptors, induces mitogenesis and differentiation of vascular endothelial cells. To understand the mechanisms underlying the VEGF-A-induced growth signaling pathway, we constructed a series of human KDR mutants and examined their biological properties. An in vitro kinase assay and subsequent tryptic peptide mapping revealed that Y1175 and Y1214 are the two major VEGF-A-dependent autophosphorylation sites. Using an antibody highly specific to the phosphoY1175 region, we demonstrated that Y1175 is phosphorylated rapidly in vivo in primary endothelial cells. When the mutated KDRs were introduced into the endothelial cell lines by adenoviral vectors, only the Y1175F KDR, Tyr1175 to phenylalanine mutant, lost the ability to tyrosine phosphorylate phospholipase C-gamma and, significantly, reduced MAP kinase phosphorylation and DNA synthesis in response to VEGF-A. Furthermore, primary endothelial cells microinjected with anti-phosphoY1175 antibody clearly decreased DNA synthesis compared with control cells. These findings strongly suggest that autophosphorylation of Y1175 on KDR is crucial for endothelial cell proliferation, and that this region is a new target for anti-angiogenic reagents.
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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.