ArticleThe Journal of biological chemistry2006
A single amino acid substitution in the activation loop defines the decoy characteristic of VEGFR-1/FLT-1.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 87 citations in OpenAlex.
- Receptor tyrosine kinase signaling in mammalian eye development.Developmental biology · 2026Review
- Vascular Patterning affects Intramembranous Ossification through HIF1α-Vegf Signaling.bioRxiv : the preprint server for biology · 2025Article
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- Emerging Nanomedicine Approaches in Targeted Lung Cancer Treatment.International journal of molecular sciences · 2024Review
- Molecular basis of VEGFR1 autoinhibition at the plasma membrane.Nature communications · 2024Article
- Homeostatic Regulation of Pro-Angiogenic and Anti-Angiogenic Proteins via Hedgehog, Notch Grid, and Ephrin Signaling in Tibial Dyschondroplasia.Animals : an open access journal from MDPI · 2023Review
- Biology and therapeutic targeting of vascular endothelial growth factor A.Nature reviews. Molecular cell biology · 2023Review
- Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer.Cancers · 2023Review
- Promotion effect of angelica sinensis extract on angiogenesis of chicken preovulatory follicles in vitro.Poultry science · 2022Article
- Retinopathy of prematurity shows alterations in VegfaPediatric research · 2022Article
- VEGFR1 signaling in retinal angiogenesis and microinflammation.Progress in retinal and eye research · 2021Review
- Pro- and Antiangiogenic Factors in Gliomas: Implications for Novel Therapeutic Possibilities.International journal of molecular sciences · 2021Review
- The PFKFB3 Inhibitor AZ67 Inhibits Angiogenesis Independently of Glycolysis Inhibition.International journal of molecular sciences · 2021Article
- Sulfated glycans engage the Ang-Tie pathway to regulate vascular development.Nature chemical biology · 2021Article
- Article
- CD146, from a melanoma cell adhesion molecule to a signaling receptor.Signal transduction and targeted therapy · 2020Review
- VEGF-A in Cardiomyocytes and Heart Diseases.International journal of molecular sciences · 2020Review
- Structural and Functional Remodeling of the Brain Vasculature Following Stroke.Frontiers in physiology · 2020Review
- MMP14-Containing Exosomes Cleave VEGFR1 and Promote VEGFA-Induced Migration and Proliferation of Vascular Endothelial Cells.Investigative ophthalmology & visual science · 2019Article
- Alternative Splicing in Angiogenesis.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
VEGFR-1 is a kinase-defective receptor tyrosine kinase (RTK) and negatively modulates angiogenesis by acting as a decoy receptor. The decoy characteristic of VEGFR-1 is required for normal development and angiogenesis. To date, there is no molecular explanation for this unusual characteristic of VEGFR-1. Here we show that the molecular mechanisms underlying the decoy characteristic of VEGFR-1 is linked to the replacement of a highly conserved amino acid residue in the activation loop. This amino acid is highly conserved among all the type III RTKs and corresponds to aspartic acid, but in VEGFR-1 it is substituted to asparagine. Mutation of asparagine (Asn(1050)) within the activation loop to aspartic acid promoted enhanced ligand-dependent tyrosine autophosphorylation and kinase activation in vivo and in vitro. The mutant VEGFR-1 (Asp(1050)) promoted endothelial cell proliferation but not tubulogenesis. It also displayed an oncogenic phenotype as its expression in fibroblast cells elicited transformation and colony growth. Furthermore, mutation of the invariable aspartic acid to asparagine in VEGFR-2 lowered the autophosphorylation of activation loop tyrosines 1052 and 1057. We propose that the conserved aspartic acid in the activation loop favors the transphosphorylation of the activation loop tyrosines, and its absence renders RTK to a less potent enzyme by disfavoring transphosphorylation of activation loop tyrosines.
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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.