ArticlePLoS computational biology2017
Computational investigation of sphingosine kinase 1 (SphK1) and calcium dependent ERK1/2 activation downstream of VEGFR2 in endothelial cells.
Article in PLoS computational biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Comprehensive evaluation of angiogenesis-associated genes in papillary thyroid cancer using bulk RNA and single-cell sequencing data.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- Article
- Paeonol Inhibits the MAPK Signaling Pathway by Targeting SIRT1 in AGE-Induced HUVECs Injury.Combinatorial chemistry & high throughput screening · 2026Article
- Integrated bulk and single-cell transcriptomics with experimental validation to identify calmodulin-related prognostic genes in lung adenocarcinoma.American journal of cancer research · 2026Article
- Article
- Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway.Frontiers in physiology · 2024Article
- Assessment of the Effects of Sphingosine Kinase 1/Sphingosine-1-Phosphate on Microangiogenesis at Rat Myofascial Trigger Points Using Contrast-Enhanced Ultrasonography.Journal of pain research · 2024Article
- Combining Multikinase Tyrosine Kinase Inhibitors Targeting the Vascular Endothelial Growth Factor and Cluster of Differentiation 47 Signaling Pathways Is Predicted to Increase the Efficacy of Antiangiogenic Combination Therapies.ACS pharmacology & translational science · 2023Article
- Mechanistic characterization of endothelial sprouting mediated by pro-angiogenic signaling.Microcirculation (New York, N.Y. : 1994) · 2022Article
- Mechanistic regulation of SPHK1 expression and translocation by EMAP II in pulmonary smooth muscle cells.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Article
- Follicle-stimulating hormone promotes the proliferation of epithelial ovarian cancer cells by activating sphingosine kinase.Scientific reports · 2020Article
- Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia.PloS one · 2020Article
- Endothelial CaInternational journal of molecular sciences · 2019Review
- Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma.NPJ systems biology and applications · 2019Article
- 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
- Modeling triple-negative breast cancer heterogeneity: Effects of stromal macrophages, fibroblasts and tumor vasculature.Journal of theoretical biology · 2018Article
- Calcium as a signal integrator in developing epithelial tissues.Physical biology · 2018Review
- Computer Simulation of TSP1 Inhibition of VEGF-Akt-eNOS: An Angiogenesis Triple Threat.Frontiers in physiology · 2018Article
- Sphingosine Kinase 1 and Sphingosine-1-Phosphate Signaling in Colorectal Cancer.International journal of molecular sciences · 2017Review
- Hispidulin suppresses tumor growth and metastasis in renal cell carcinoma by modulating ceramide-sphingosine 1-phosphate rheostat.American journal of cancer research · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Vascular endothelial growth factor (VEGF) is a powerful regulator of neovascularization. VEGF binding to its cognate receptor, VEGFR2, activates a number of signaling pathways including ERK1/2. Activation of ERK1/2 is experimentally shown to involve sphingosine kinase 1 (SphK1) activation and its calcium-dependent translocation downstream of ERK1/2. Here we construct a rule-based computational model of signaling downstream of VEGFR2, by including SphK1 and calcium positive feedback mechanisms, and investigate their consequences on ERK1/2 activation. The model predicts the existence of VEGF threshold in ERK1/2 activation that can be continuously tuned by cellular concentrations of SphK1 and sphingosine 1 phosphate (S1P). The computer model also predicts powerful effects of perturbations in plasma and ER calcium pump rates and the current through the CRAC channels on ERK1/2 activation dynamics, highlighting the critical role of intracellular calcium in shaping the pERK1/2 signal. The model is then utilized to simulate anti-angiogenic therapeutic interventions targeting VEGFR2-ERK1/2 axis. Simulations indicate that monotherapies that exclusively target VEGFR2 phosphorylation, VEGF, or VEGFR2 are ineffective in shutting down signaling to ERK1/2. By simulating therapeutic strategies that target multiple nodes of the pathway such as Raf and SphK1, we conclude that combination therapy should be much more effective in blocking VEGF signaling to EKR1/2. The model has important implications for interventions that target signaling pathways in angiogenesis relevant to cancer, vascular diseases, and wound healing.
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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 Socratic graph.