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Lipid Raft Association Stabilizes VEGF Receptor 2 in Endothelial Cells.
Zabroski, Ibukunoluwapo O; Nugent, Matthew A.
Afiliación
  • Zabroski IO; Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.
  • Nugent MA; Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Int J Mol Sci ; 22(2)2021 Jan 14.
Article en En | MEDLINE | ID: mdl-33466887
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-ß-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microdominios de Membrana / Receptor 2 de Factores de Crecimiento Endotelial Vascular / Células Endoteliales Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microdominios de Membrana / Receptor 2 de Factores de Crecimiento Endotelial Vascular / Células Endoteliales Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza