ArticlePLoS computational biology2015
Site-Specific Phosphorylation of VEGFR2 Is Mediated by Receptor Trafficking: Insights from a Computational Model.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 56 citations in OpenAlex.
- VEGFAngiogenesis · 2026Article
- Strain Promotes Triple Negative Breast Cancer Proliferation and Migration Via VEGFR-2.Cellular and molecular bioengineering · 2025Article
- Endothelial-Pericyte Interactions Regulate Angiogenesis Via VEGFR2 Signaling During Retinal Development and Disease.Investigative ophthalmology & visual science · 2025Article
- Impact of ligand binding on VEGFR1, VEGFR2, and NRP1 localization in human endothelial cells.PLoS computational biology · 2025Article
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Quantification of surface-localized and total oxytocin receptor in myometrial smooth muscle cells.Heliyon · 2024Article
- Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells.PLoS computational biology · 2024Article
- Wnt7a deficit is associated with dysfunctional angiogenesis in pulmonary arterial hypertension.The European respiratory journal · 2023Article
- KIF13B mediates VEGFR2 recycling to modulate vascular permeability.Cellular and molecular life sciences : CMLS · 2023Article
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- AGGF1 Shows the α5β1 Integrin to Be AnotherArteriosclerosis, thrombosis, and vascular biology · 2021Article
- TKI-Resistant Renal Cancer Secretes Low-Level Exosomal miR-549a to Induce Vascular Permeability and Angiogenesis to Promote Tumor Metastasis.Frontiers in cell and developmental biology · 2021Article
- VEGF-A splice variants bind VEGFRs with differential affinities.Scientific reports · 2020Article
- Elements of the Endomucin Extracellular Domain Essential for VEGF-Induced VEGFR2 Activity.Cells · 2020Article
- No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells.The Journal of biological chemistry · 2019Article
- Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Corosolic acid impairs human lung adenocarcinoma A549 cells proliferation by inhibiting cell migration.Oncology letters · 2019Article
- Context-dependent regulation of receptor tyrosine kinases: Insights from systems biology approaches.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Tumor and endothelial cells collaborate via transcellular receptor complexes.The Journal of pathology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Matrix-binding isoforms and non-matrix-binding isoforms of vascular endothelial growth factor (VEGF) are both capable of stimulating vascular remodeling, but the resulting blood vessel networks are structurally and functionally different. Here, we develop and validate a computational model of the binding of soluble and immobilized ligands to VEGF receptor 2 (VEGFR2), the endosomal trafficking of VEGFR2, and site-specific VEGFR2 tyrosine phosphorylation to study differences in induced signaling between these VEGF isoforms. In capturing essential features of VEGFR2 signaling and trafficking, our model suggests that VEGFR2 trafficking parameters are largely consistent across multiple endothelial cell lines. Simulations demonstrate distinct localization of VEGFR2 phosphorylated on Y1175 and Y1214. This is the first model to clearly show that differences in site-specific VEGFR2 activation when stimulated with immobilized VEGF compared to soluble VEGF can be accounted for by altered trafficking of VEGFR2 without an intrinsic difference in receptor activation. The model predicts that Neuropilin-1 can induce differences in the surface-to-internal distribution of VEGFR2. Simulations also show that ligated VEGFR2 and phosphorylated VEGFR2 levels diverge over time following stimulation. Using this model, we identify multiple key levers that alter how VEGF binding to VEGFR2 results in different coordinated patterns of multiple downstream signaling pathways. Specifically, simulations predict that VEGF immobilization, interactions with Neuropilin-1, perturbations of VEGFR2 trafficking, and changes in expression or activity of phosphatases acting on VEGFR2 all affect the magnitude, duration, and relative strength of VEGFR2 phosphorylation on tyrosines 1175 and 1214, and they do so predictably within our single consistent model framework.
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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.