The recombinant kringle domain of urokinase plasminogen activator inhibits VEGF165-induced angiogenesis of HUVECs by suppressing VEGFR2 dimerization and subsequent signal transduction.
IUBMB Life
; 64(3): 259-65, 2012 Mar.
Article
en En
| MEDLINE
| ID: mdl-22252975
ABSTRACT
The recombinant kringle domain (UK1) of urokinase plasminogen activator was previously reported to exert antiangiogenic activity against Vascular Endothelial Growth Factor (VEGF)-induced angiogenesis in both in vitro and in vivo models. In this study, we explored the molecular signaling mechanisms involved in the antiangiogenic activity of UK1 by examining VEGF signaling proteins. VEGF165 stimulates the phosphorylation of VEGF signaling molecules, and pretreatment with UK1 blocked VEGF-induced signal transduction associated with proliferation, survival, and migration. UK1 also suppressed VEGF165-induced activation of MMP-2. Moreover, UK1 suppressed the phosphorylation and activation of VEGFR2 in VEGF-stimulated human umbilical cord vein endothelial cells (HUVECs) by blocking the dimerization of VEGFR2. Overall, our findings suggest that UK1 inhibits VEGF-induced proliferation, migration, and matrix metalloproteinase activity of HUVECs by suppressing VEGFR2 dimerization and subsequent angiogenic signals.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes
/
Activador de Plasminógeno de Tipo Uroquinasa
/
Transducción de Señal
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Neovascularización Fisiológica
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Receptor 2 de Factores de Crecimiento Endotelial Vascular
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Factor A de Crecimiento Endotelial Vascular
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Células Endoteliales de la Vena Umbilical Humana
Límite:
Humans
Idioma:
En
Revista:
IUBMB Life
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2012
Tipo del documento:
Article