Vascular endothelial growth factor receptor-3 activity is modulated by its association with caveolin-1 on endothelial membrane.
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.
Galvagni
Federico
F
Dipartimento di Biologia Molecolare, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy.
Anselmi
Francesca
F
Salameh
Ahmad
A
Orlandini
Maurizio
M
Rocchigiani
Marina
M
Oliviero
Salvatore
S
D000818:Animals; D001549:Benzamides; D021941:Caveolae / Q000737:chemistry; D051242:Caveolin 1 / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D002999:Clone Cells; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D000068877:Imatinib Mesylate; D008221:Lymphoid Tissue / Q000737:chemistry; D051379:Mice; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D034421:Sus scrofa; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000187:drug effects* / Q000378:metabolism*
C412373:AG 1879; D001549:Benzamides; D051242:Caveolin 1; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D040321:Vascular Endothelial Growth Factor Receptor-3; D016315:Proto-Oncogene Proteins c-abl; D016392:Proto-Oncogene Proteins pp60(c-src)