Vascular endothelial growth factor receptor-3 (VEGFR-3) is constitutively expressed in lymphatic vessels and transiently in endothelial cells of blood vessels during angiogenesis. Here we report that VEGFR-3 localizes in the caveolae membrane of endothelial cells and co-immunoprecipitates with caveolin-1. Caveolin-1 silencing or its depletion from the cell membrane by cholesterol increases VEGFR-3 autophosphorylation, suggesting that caveolin acts as a negative regulator of VEGFR-3 activity. Receptor activation induces caveolin-1 phosphorylation on tyrosine residues including tyrosine 14. Cell treatment with Src or Abl inhibitors PP2 or STI571, prior to receptor stimulation, affects caveolin-1 phosphorylation without affecting receptor autophosphorylation, suggesting that both Src and Abl are involved in VEGFR-3-dependent caveolin-1 phosphorylation. Caveolin-1 phosphorylation in Src/Fyn/Yes knockout cells demonstrated that Abl phosphorylates caveolin-1 independently from Src family members. These results suggest a functional interaction between VEGFR-3 and caveolin-1 to modulate endothelial cell activation during angiogenesis.
|Titolo:||Vascular endothelial growth factor receptor-3 activity is modulated by its association with caveolin-1 on endothelial membrane.|
|Citazione:||Galvagni, F., Anselmi, F., Salameh, A., Orlandini, M., Rocchigiani, M., & Oliviero, S. (2007). Vascular endothelial growth factor receptor-3 activity is modulated by its association with caveolin-1 on endothelial membrane. BIOCHEMISTRY, 46, 3998-4005.|
|Appare nelle tipologie:||1.1 Articolo in rivista|
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