期刊
IUBMB LIFE
卷 64, 期 3, 页码 259-265出版社
WILEY
DOI: 10.1002/iub.604
关键词
recombinant kringle domain (UK1) of urokinase plasminogen activator (uPA); HUVEC; proliferation; migration; matrix metalloproteinases (MMPs); VEGFR2 dimerization
资金
- Ministry of Education, Science and Technology (MEST) of the Republic of Korea
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. (c) 2012 IUBMB IUBMB Life, 2012
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