VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation

Hayashi, Makoto and Majumdar, Arindam and Li, Xiujuan and Adler, Jeremy and Sun, Zuyue and Vertuani, Simona and Hellberg, Carina and Mellberg, Sofie and Koch, Sina and Dimberg, Anna and Young Koh, Gou and Dejana, Elisabetta and Belting, Heinz-Georg and Affolter, Markus and Thurston, Gavin and Holmgren, Lars and Vestweber, Dietmar and Claesson-Welsh, Lena. (2013) VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation. Nature communications, Vol. 4 , Article Nr. 1672. p. 1672.

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Official URL: http://edoc.unibas.ch/dok/A6124446

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Vascular endothelial growth factor (VEGF) guides the path of new vessel sprouts by inducing VEGF receptor-2 activity in the sprout tip. In the stalk cells of the sprout, VEGF receptor-2 activity is downregulated. Here, we show that VEGF receptor-2 in stalk cells is dephosphorylated by the endothelium-specific vascular endothelial-phosphotyrosine phosphatase (VE-PTP). VE-PTP acts on VEGF receptor-2 located in endothelial junctions indirectly, via the Angiopoietin-1 receptor Tie2. VE-PTP inactivation in mouse embryoid bodies leads to excess VEGF receptor-2 activity in stalk cells, increased tyrosine phosphorylation of VE-cadherin and loss of cell polarity and lumen formation. Vessels in ve-ptp(-/-) teratomas also show increased VEGF receptor-2 activity and loss of endothelial polarization. Moreover, the zebrafish VE-PTP orthologue ptp-rb is essential for polarization and lumen formation in intersomitic vessels. We conclude that the role of Tie2 in maintenance of vascular quiescence involves VE-PTP-dependent dephosphorylation of VEGF receptor-2, and that VEGF receptor-2 activity regulates VE-cadherin tyrosine phosphorylation, endothelial cell polarity and lumen formation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Affolter)
UniBasel Contributors:Affolter, Markus
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:23
Deposited On:24 May 2013 09:18

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