ArticleCellular signalling2013
Computational model of VEGFR2 pathway to ERK activation and modulation through receptor trafficking.
Article in Cellular signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Impact of ligand binding on VEGFR1, VEGFR2, and NRP1 localization in human endothelial cells.PLoS computational biology · 2025Article
- CD133-containing microvesicles promote colorectal cancer progression by inducing tumor angiogenesis.Heliyon · 2024Article
- Trafficking dynamics of VEGFR1, VEGFR2, and NRP1 in human endothelial cells.PLoS computational biology · 2024Article
- Non-Muscle MLCK Contributes to Endothelial Cell Hyper-Proliferation through the ERK Pathway as a Mechanism for Vascular Remodeling in Pulmonary Hypertension.International journal of molecular sciences · 2022Article
- Brain arteriovenous malformation in hereditary hemorrhagic telangiectasia: Recent advances in cellular and molecular mechanisms.Frontiers in human neuroscience · 2022Review
- DHA-enriched phosphatidylcholine suppressed angiogenesis by activating PPARγ and modulating the VEGFR2/Ras/ERK pathway in human umbilical vein endothelial cells.Food science and biotechnology · 2021Article
- Safranal Inhibits AngiogenesisFrontiers in oncology · 2021Article
- ERK and Akt exhibit distinct signaling responses following stimulation by pro-angiogenic factors.Cell communication and signaling : CCS · 2020Article
- Mathematical Model Predicts Effective Strategies to Inhibit VEGF-eNOS Signaling.Journal of clinical medicine · 2020Article
- Mechanistic insight into activation of MAPK signaling by pro-angiogenic factors.BMC systems biology · 2018Article
- Computational modeling of synergistic interaction between αVβ3 integrin and VEGFR2 in endothelial cells: Implications for the mechanism of action of angiogenesis-modulating integrin-binding peptides.Journal of theoretical biology · 2018Article
- Quantifying the phosphorylation timescales of receptor-ligand complexes: a Markovian matrix-analytic approach.Open biology · 2018Article
- The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment.Integrative biology : quantitative biosciences from nano to macro · 2018Article
- Computer Simulation of TSP1 Inhibition of VEGF-Akt-eNOS: An Angiogenesis Triple Threat.Frontiers in physiology · 2018Article
- VEGFR1 promotes cell migration and proliferation through PLCγ and PI3K pathways.NPJ systems biology and applications · 2018Article
- Fibronectin fibrils regulate TGF-β1-induced Epithelial-Mesenchymal Transition.Matrix biology : journal of the International Society for Matrix Biology · 2017Article
- Computational investigation of sphingosine kinase 1 (SphK1) and calcium dependent ERK1/2 activation downstream of VEGFR2 in endothelial cells.PLoS computational biology · 2017Article
- VEGF regulates local inhibitory complement proteins in the eye and kidney.The Journal of clinical investigation · 2017Article
- Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK Pathway.Frontiers in cellular neuroscience · 2017Article
- Selective Targeting of a Novel Epsin-VEGFR2 Interaction Promotes VEGF-Mediated Angiogenesis.Circulation research · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular Endothelial Growth Factor (VEGF) signal transduction is central to angiogenesis in development and in pathological conditions such as cancer, retinopathy and ischemic diseases. We constructed and validated a computational model of VEGFR2 trafficking and signaling, to study the role of receptor trafficking kinetics in modulating ERK phosphorylation in VEGF-stimulated endothelial cells. Trafficking parameters were optimized and validated against four previously published in vitro experiments. Based on these parameters, model simulations demonstrated interesting behaviors that may be highly relevant to understanding VEGF signaling in endothelial cells. First, at moderate VEGF doses, VEGFR2 phosphorylation and ERK phosphorylation are related in a log-linear fashion, with a stable duration of ERK activation; but with higher VEGF stimulation, phosphoERK becomes saturated, and its duration increases. Second, a large endosomal fraction of VEGFR2 makes the ERK activation reaction network less sensitive to perturbations in VEGF dosage. Third, extracellular-matrix-bound VEGF binds and activates VEGFR2, but by internalizing at a slower rate, matrix-bound VEGF-induced intracellular ERK phosphorylation is predicted to be greater in magnitude and more sustained, in agreement with experimental evidence. Fourth, different endothelial cell types appear to have different trafficking rates, which result in different levels of endosomal receptor localization and different ERK response profiles.
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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.