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H. Lee, C. Sunil, S. Daniel, H. Amir, R. Dana; A Novel Tyrosine Kinase-Based Signal Pathway for Regulation of Hemangiogenesis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4972.
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© ARVO (1962-2015); The Authors (2016-present)
Pseudokinases are a group of proteins that lack one or more essential motifs for kinase activity and hence are predicted to be kinetically inactive. Protein tyrosine kinase 7 (PTK7) is one pseudokinase and is expressed in various types of vascular endothelial cells. The purpose of this study was to determine the expression and investigate the role of PTK7 in hemangiogenesis through the corneal micropocket assay.
To determine the expression of PTK7, we performed western immunoblot with various types of vascular endothelial cells. To clarify the relationship between PTK7 and vascular endothelial growth factor receptors (VEGFRs), immunoprecipitation and immunoblot for these receptor tyrosine kinases were performed consecutively. In addition, using insertion of a 160 ng VEGF corneal micropellet, we determined the effect of PTK7 in VEGF-induced corneal neovascularization.
PTK7 was highly expressed in various types of vascular endothelial cells. Through the IP and immunoblot, PTK7 was found to join the receptor complex with VEGFR1, but not with VEGFR2 or -R3. The VEGFR1 induced downstream signal was downregulated by inhibition of PTK7 using siRNA. We found significant numbers of PTK7+ cells in the neovasculature and its surrounding stromal areas in the corneal micropellet assay. The corneal neovascularization induced by VEGF-A was significantly decreased by subconjunctival injection of siRNA for PTK7.
Our data suggest that PTK7 serves as a co-receptor for activation of VEGFR1 and is an important factor for VEGFR1 induced downstream signaling in hemangiogenesis. PTK7 mediated VEGFR1 signaling may also regulate the migratory activity of vascular endothelial cells.
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