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

Vertuani, Simona (author)

Hellberg, Carina (author)

Koh, Gou Young (author)

Dejana, Elisabetta (author)

Belting, Heinz-Georg (author)

Affolter, Markus (author)

Thurston, Gavin (author)

Vestweber, Dietmar (author)

Claesson-Welsh, Lena (author): Uppsala universitet,Cancer och vaskulärbiologi

(creator_code:org_t)

2013-04-09
2013
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 1672-

Related links:: https://www.nature.c...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

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.

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