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Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway

Authors
 Hyung Keun Lee ; Sunil K. Chauhan ; Reza Dana ; EunDuk Kay 
Citation
 Blood, Vol.117(21) : 5762~5771, 2011 
Journal Title
 Blood 
ISSN
 0006-4971 
Issue Date
2011
Abstract
Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), but not with KDR/Flk-1 (VEGFR2) or with Flt-4 (VEGFR3). By surface plasmon resonance analysis, the interaction between Flt-1 and PTK7 was confirmed and found to be intensified by VEGF-A. Flt-1 phosphorylation and downstream signals of Akt, and focal adhesion kinase (FAK) thus induced were down-regulated by inhibition of PTK7 expression using siRNA. Moreover, PTK7 overexpression in endothelial cells resulted in enhanced angiogenesis in vitro. In contrast, neovascularization induced in vivo by VEGF-A pellets was significantly decreased by injection of siRNA targeting PTK7. These data suggest that PTK7 serves an essential role in Flt-1-mediated angiogenesis.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94859
DOI
10.1182/blood-2010-09-306928
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Ophthalmology
Yonsei Authors
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