Lipid Raft Association Stabilizes VEGF Receptor 2 in Endothelial Cells
| Autor: | Matthew A. Nugent, Ibukunoluwapo O Zabroski |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine MAPK/ERK pathway Angiogenesis receptor lcsh:Chemistry angiogenesis chemistry.chemical_compound 0302 clinical medicine simvastatin Extracellular Signal-Regulated MAP Kinases lcsh:QH301-705.5 Lipid raft Cells Cultured Spectroscopy lipid rafts vascular endothelial growth factor Protein Stability Anticholesteremic Agents General Medicine respiratory system Computer Science Applications Cell biology Vascular endothelial growth factor Endothelial stem cell Vascular endothelial growth factor A 030220 oncology & carcinogenesis endothelial cell lysosome cardiovascular system lipids (amino acids peptides and proteins) Signal transduction Sphingomyelin Protein Binding Signal Transduction circulatory and respiratory physiology Article Catalysis Inorganic Chemistry 03 medical and health sciences Membrane Microdomains Animals Humans Physical and Theoretical Chemistry Molecular Biology Organic Chemistry Endothelial Cells cholesterol Vascular Endothelial Growth Factor Receptor-2 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 chemistry Blood Vessels Cattle |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 2 International Journal of Molecular Sciences, Vol 22, Iss 798, p 798 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22020798 |
| Popis: | The binding of vascular endothelial growth factor A (VEGF) to VEGF receptor-2 (VEGFR-2) stimulates angiogenic signaling. Lipid rafts are cholesterol-dense regions of the plasma membrane that serve as an organizational platform for biomolecules. Although VEGFR2 has been shown to colocalize with lipid rafts to regulate its activation, the effect of lipid rafts on non-activated VEGFR2 has not been explored. Here, we characterized the involvement of lipid rafts in modulating the stability of non-activated VEGFR2 in endothelial cells using raft disrupting agents: methyl-&beta cyclodextrin, sphingomyelinase and simvastatin. Disrupting lipid rafts selectively decreased the levels of non-activated VEGFR2 as a result of increased lysosomal degradation. The decreased expression of VEGFR2 translated to reduced VEGF-activation of the extracellular signal-regulated protein kinases (ERK). Overall, our results indicate that lipid rafts stabilize VEGFR2 and its associated signal transduction activities required for angiogenesis. Thus, modulation of lipid rafts may provide a means to regulate the sensitivity of endothelial cells to VEGF stimulation. Indeed, the ability of simvastatin to down regulate VEGFR2 and inhibit VEGF activity suggest a potential mechanism underlying the observation that this drug improves outcomes in the treatment of certain cancers. |
| Databáze: | OpenAIRE |
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