ArticleThe Journal of biological chemistry2016
Constitutive Endocytosis of VEGFR2 Protects the Receptor against Shedding.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Modeling the synovium on a chip for studying the interactions between lymphatic vasculature and synoviocytes in rheumatoid arthritis.Biofabrication · 2026Article
- VEGFR2 dimerization kinetics on the cell surface determined by microscopy and mathematical modeling.Biophysical journal · 2026Article
- Humanized Murine Glioblastoma Models for Evaluation of Coxsackievirus Oncolytic Therapy.Cancers · 2026Article
- Evaluating VEGFR2 as a Target for Anti-Tumour Therapy in Canine Melanoma.Veterinary and comparative oncology · 2026Article
- Fenestrated Endothelial Cells across Organs: Insights into Kidney Function and Disease.International journal of molecular sciences · 2024Review
- Molecular basis of VEGFR1 autoinhibition at the plasma membrane.Nature communications · 2024Article
- Epsin Endocytic Adaptor Proteins in Angiogenic and Lymphangiogenic Signaling.Cold Spring Harbor perspectives in medicine · 2024Review
- A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension.European heart journal · 2023Article
- KIF13B mediates VEGFR2 recycling to modulate vascular permeability.Cellular and molecular life sciences : CMLS · 2023Article
- Characteristic Features of Deep Brain Lymphatic Vessels and Their Regulation by Chronic Stress.Research (Washington, D.C.) · 2023Article
- Rab GTPases as Modulators of Vascular Function.Cells · 2022Review
- Trafficking in blood vessel development.Angiogenesis · 2022Review
- Mediating EGFR-TKI Resistance by VEGF/VEGFR Autocrine Pathway in Non-Small Cell Lung Cancer.Cells · 2022Article
- A role for Flower and cell death in controlling morphogen gradient scaling.Nature cell biology · 2022Article
- Robo4 is constitutively shed by ADAMs from endothelial cells and the shed Robo4 functions to inhibit Slit3-induced angiogenesis.Scientific reports · 2022Article
- A Single Short 'Tone Burst' Results in Optimal Drug Delivery to Tumours Using Ultrasound-Triggered Therapeutic Microbubbles.Pharmaceutics · 2022Article
- Article
- Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Article
- Lipid Raft Association Stabilizes VEGF Receptor 2 in Endothelial Cells.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VEGFR2 plays a fundamental role in blood vessel formation and in life threatening diseases, such as cancer angiogenesis and cardiovascular disorders. Although inactive growth factor receptors are mainly localized at the plasma membrane, VEGFR2 undergoes constitutive endocytosis (in the absence of ligand) and recycling. Intriguingly, the significance of these futile transport cycles of VEGFR2 remains unclear. Here we found that, unexpectedly, the function of constitutive endocytosis of VEGFR2 is to protect the receptor against plasma membrane cleavage (shedding), thereby preserving the functional state of the receptor until the time of activation by VEGF. Inhibition of constitutive endocytosis of VEGFR2, by interference with the function of clathrin, dynamin, or Rab5, increases dramatically the cleavage/shedding of VEGFR2. Shedding of VEGFR2 produces an N-terminal soluble fragment (100 kDa, s100), which is released in the extracellular space, and a residual C-terminal part (130 kDa, p130) that remains integrated at the plasma membrane. The released soluble fragment (s100) co-immunoprecipitates with VEGF, in line with the topology of the VEGF-binding domain at the N terminus of VEGFR2. Increased shedding of VEGFR2 (via inhibition of constitutive endocytosis) results in reduced response to VEGF, consistently with the loss of the VEGF-binding domain from the membrane remnant of VEGFR2. These data suggest that constitutive internalization of VEGFR2 protects the receptor against shedding and provides evidence for an unprecedented mechanism via which endocytosis can regulate the fate and activity of growth factor receptors.
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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.