ArticleThe Journal of biological chemistry2009
Vascular endothelial growth factor (VEGF) receptor-2 tyrosine 1175 signaling controls VEGF-induced von Willebrand factor release from endothelial cells via phospholipase C-gamma 1- and protein kinase A-dependent pathways.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- VEGF-A in COVID-19: a systematic review and meta-analytical approach to its prognostic value.Clinical and experimental medicine · 2025Pooled it
- Shock Induced Endotheliopathy and High Trauma Mortality-Fight-or-Flight Response Revisited.International journal of molecular sciences · 2026Review
- Article
- Vascular endothelial generating factor pathway in ovarian cancer.Journal of ovarian research · 2025Review
- Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players.Stem cell research & therapy · 2025Review
- Factor VIII as a potential player in cancer pathophysiology.Journal of thrombosis and haemostasis : JTH · 2022Article
- Spire1 and Myosin Vc promote CaCellular and molecular life sciences : CMLS · 2022Article
- Local delivery of hydrogel encapsulated vascular endothelial growth factor for the prevention of medication-related osteonecrosis of the jaw.Scientific reports · 2021Article
- Therapeutic potential of mesenchymal stem cells for peripheral artery disease in a rat model of hindlimb ischemia.Iranian journal of basic medical sciences · 2021Article
- Experimental pathology by intravital microscopy and genetically encoded fluorescent biosensors.Pathology international · 2020Review
- Rab46 integrates CaThe Journal of cell biology · 2019Article
- The Role of Angiogenesis and Pro-Angiogenic Exosomes in Regenerative Dentistry.International journal of molecular sciences · 2019Review
- Exocytosis of Weibel-Palade bodies: how to unpack a vascular emergency kit.Journal of thrombosis and haemostasis : JTH · 2019Review
- Recovery of Neurovascular Unit Integrity by CDK5-KD Astrocyte Transplantation in a Global Cerebral Ischemia Model.Molecular neurobiology · 2018Article
- VEGF regulates local inhibitory complement proteins in the eye and kidney.The Journal of clinical investigation · 2017Article
- mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma after multi-walled carbon nanotube inhalation exposure in mice.Journal of applied toxicology : JAT · 2016Article
- Gastric cancer-associated enhancement of von Willebrand factor is regulated by vascular endothelial growth factor and related to disease severity.BMC cancer · 2015Article
- VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- VEGF-VEGFR Signals in Health and Disease.Biomolecules & therapeutics · 2014Review
- VEGFR and type-V RTK activation and signaling.Cold Spring Harbor perspectives in biology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is increasing evidence that vascular endothelial growth factor (VEGF) contributes to inflammation independent of its angiogenic functions. Targeting some of the components in endothelial Weibel-Palade bodies (WPBs) effectively inhibits VEGF-induced inflammation, but little is known about how VEGF regulates WPB exocytosis. In this study, we showed that VEGF receptor-2 (VEGFR2), but not VEGFR1, is responsible for VEGF-induced release of von Willebrand factor (vWF), a major marker of WPBs. This is in good contrast to VEGF-stimulated interleukin-6 release from endothelium, which is selectively mediated through VEGFR1. We further demonstrated that VEGFR2-initiated phospholipase C-gamma1 (PLCgamma1)/calcium signaling is important but insufficient for full vWF release, suggesting the possible participation of another effector pathway. We found that cAMP/protein kinase A (PKA) signaling is required for full vWF release. Importantly, a single mutation of Tyr(1175) in the C terminus of VEGFR2, a tyrosine residue crucial for embryonic vasculogenesis, abolished vWF release, concomitant with defective activations of both PLCgamma1 and PKA. These data suggest that Tyr(1175) mediates both PLCgamma1-dependent and PKA-dependent signaling pathways. Taken together, our results not only reveal a novel Tyr(1175)-mediated signaling pathway but also highlight a potentially new therapeutic target for the management of vascular inflammation.
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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.