ArticleOncogene1999
VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers, 2 of them syntheses that pooled it.
What it found
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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
196 citing papers in PubMed, 2 syntheses or guidelines pooled it, 573 citations in OpenAlex.
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- Treatment Strategies of Gastric Cancer-Molecular Targets for Anti-angiogenic Therapy: a State-of-the-art Review.Journal of gastrointestinal cancer · 2021Pooled it
- A phase II study of sorafenib in malignant mesothelioma: results of Cancer and Leukemia Group B 30307.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2010Trial
- Targeting vascular endothelial growth factor (VEGF)-induced angiogenesis withNutrition research and practice · 2026Article
- Wnt10a exhibit spatiotemporal singularity in the temporal changes of angiogenesis in regenerated pulp-like tissue.Inflammation and regeneration · 2026Article
- Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Strategies for the vascular patterning of engineered tissues for organ repair.Nature biomedical engineering · 2025Review
- Applying Computational Protein Design to Engineer Affibodies for Affinity-controlled Delivery of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor.Biomacromolecules · 2025Article
- Human umbilical cord mesenchymal stem cells improve the survial of flaps by promoting angiogenesis in mice.European journal of medical research · 2025Article
- Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance.Archives of pharmacal research · 2025Review
- Advances in Targeted and Chemotherapeutic Strategies for Colorectal Cancer: Current Insights and Future Directions.Biomedicines · 2025Review
- Exercise-mediated cerebrovascular repair in Alzheimer's disease: from pathophysiology to therapeutic precision.Frontiers in aging neuroscience · 2025Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- The potential role of Ral-interacting protein 76 and vascular endothelial growth factor on angiogenesis in the tumor and ovarian corpus luteum microenvironment.Translational cancer research · 2024Review
- Exploring treatment options in cancer: Tumor treatment strategies.Signal transduction and targeted therapy · 2024Review
- VEGF as a Key Actor in Recurrent Respiratory Papillomatosis: A Narrative Review.Current issues in molecular biology · 2024Review
- 2-Desaza-annomontine (C81) impedes angiogenesis through reduced VEGFR2 expression derived from inhibition of CDC2-like kinases.Angiogenesis · 2024Article
- Novel insights into cardiovascular toxicity of cancer targeted and immune therapies: Beyond ischemia with non-obstructive coronary arteries (INOCA).American heart journal plus : cardiology research and practice · 2024Article
- Estrogen-receptor status determines differential regulation of α1- and α2-adrenoceptor-mediated cell survival, angiogenesis, and intracellular signaling responses in breast cancer cell lines.Medical oncology (Northwood, London, England) · 2024Article
- Bioinformatics Prediction for Network-Based Integrative Multi-Omics Expression Data Analysis in Hirschsprung Disease.Biomolecules · 2024Article
136 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KDR/FIk-1 tyrosine kinase, one of the two VEGF receptors induces mitogenesis and differentiation of vascular endothelial cells. We have previously reported that a major target molecule of KDR/Flk-1 kinase is PLC-gamma, and that VEGF induces activation of MAP kinase, mainly mediated by protein kinase C (PKC) in the NIH3T3 cells overexpressing KDR/FIk-1 (Takahashi and Shibuya, 1997). However, the signal transduction initiated from VEGF in endothelial cells remains to be elucidated. In primary sinusoidal endothelial cells which showed strictly VEGF-dependent growth, we found that VEGF stimulated the activation of Raf-1-MEK-MAP kinase cascade. To our surprise, an important regulator, Ras was not efficiently activated to a significant level in response to VEGF. Consistent with this, dominant-negative Ras did not block the VEGF-induced phosphorylation of MAP kinase. On the other hand, PKC-specific inhibitors severely reduced VEGF-dependent phosphorylation of MEK, activation of MAP kinase and subsequent DNA synthesis. A potent PI3 kinase inhibitor, Wortmannin, could not inhibit either of them. These results suggest that in primary endothelial cells, VEGF-induced activation of Raf-MEK-MAP kinase and DNA synthesis are mainly mediated by PKC-dependent pathway, much more than by Ras-dependent or PI3 kinase-dependent pathway.
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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.