ArticleThe Journal of biological chemistry2015
R-Ras protein inhibits autophosphorylation of vascular endothelial growth factor receptor 2 in endothelial cells and suppresses receptor activation in tumor vasculature.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries.Nature genetics · 2024Article
- Akt3 activation by R-Ras in an endothelial cell enforces quiescence and barrier stability of neighboring endothelial cells via Jagged1.Cell reports · 2024Article
- Lung endothelial cells regulate pulmonary fibrosis through FOXF1/R-Ras signaling.Nature communications · 2023Article
- The Role of R-Ras Proteins in Normal and Pathologic Migration and Morphologic Change.The American journal of pathology · 2021Review
- High Endothelial Venules Accelerate Naive T Cell Recruitment by Tumor Necrosis Factor-Mediated R-Ras Upregulation.The American journal of pathology · 2021Article
- R-Ras Deficiency in Pericytes Causes Frequent Microphthalmia and Perturbs Retinal Vascular Development.Journal of vascular research · 2021Article
- Prostaglandin E2 breaks down pericyte-endothelial cell interaction via EP1 and EP4-dependent downregulation of pericyte N-cadherin, connexin-43, and R-Ras.Scientific reports · 2020Article
- MicroRNA Expression Profiling of Bone Marrow-Derived Proangiogenic Cells (PACs) in a Mouse Model of Hindlimb Ischemia: Modulation by Classical Cardiovascular Risk Factors.Frontiers in genetics · 2020Article
- Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies.Frontiers in pharmacology · 2020Review
- Response to the hunt for the perfect biomarker in nasopharyngeal carcinoma-the RRAS "race" beyond Epstein-barr virus?Translational cancer research · 2019Article
- Prolonged activation of cAMP signaling leads to endothelial barrier disruption via transcriptional repression of RRAS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- R-Ras-Akt axis induces endothelial lumenogenesis and regulates the patency of regenerating vasculature.Nature communications · 2017Article
- Targeting NRASAmerican journal of cancer research · 2017Article
- Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy.Investigative ophthalmology & visual science · 2016Article
- Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis.Scientific reports · 2016Article
- R-Ras Inhibits VEGF-Induced p38MAPK Activation and HSP27 Phosphorylation in Endothelial Cells.Journal of vascular research · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Abnormal angiogenesis is associated with a broad range of medical conditions, including cancer. The formation of neovasculature with functionally defective blood vessels significantly impacts tumor progression, metastasis, and the efficacy of anticancer therapies. Vascular endothelial growth factor (VEGF) potently induces vascular permeability and vessel growth in the tumor microenvironment, and its inhibition normalizes tumor vasculature. In contrast, the signaling of the small GTPase R-Ras inhibits excessive angiogenic growth and promotes the maturation of regenerating blood vessels. R-Ras signaling counteracts VEGF-induced vessel sprouting, permeability, and invasive activities of endothelial cells. In this study, we investigated the effect of R-Ras on VEGF receptor 2 (VEGFR2) activation by VEGF, the key mechanism for angiogenic stimulation. We show that tyrosine phosphorylation of VEGFR2 is significantly elevated in the tumor vasculature and dermal microvessels of VEGF-injected skin in R-Ras knockout mice. In cultured endothelial cells, R-Ras suppressed the internalization of VEGFR2, which is required for full activation of the receptor by VEGF. Consequently, R-Ras strongly suppressed autophosphorylation of the receptor at all five major tyrosine phosphorylation sites. Conversely, silencing of R-Ras resulted in increased VEGFR2 phosphorylation. This effect of R-Ras on VEGFR2 was, at least in part, dependent on vascular endothelial cadherin. These findings identify a novel function of R-Ras to control the response of endothelial cells to VEGF and suggest an underlying mechanism by which R-Ras regulates angiogenesis.
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Registered trials
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