VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation
- Authors
- Hayashi, M., Majumdar, A., Li, X., Adler, J., Sun, Z., Vertuani, S., Hellberg, C., Mellberg, S., Koch, S., Dimberg, A., Young Koh, G., Dejana, E., Belting, H.G., Affolter, M., Thurston, G., Holmgren, L., Vestweber, D., and Claesson-Welsh, L.
- ID
- ZDB-PUB-130418-14
- Date
- 2013
- Source
- Nature communications 4: 1672 (Journal)
- Registered Authors
- Affolter, Markus, Belting, Heinz-Georg Paul (Henry), Holmgren, Lars, Majumdar, Arindam
- Keywords
- Cardiovascular biology, Cell signalling, Developmental biology
- MeSH Terms
-
- Animals
- Cell Polarity*
- Endothelium, Vascular/cytology*
- Endothelium, Vascular/enzymology
- Endothelium, Vascular/metabolism
- Intercellular Junctions
- Mice
- Phosphorylation
- Receptor, TIE-2/metabolism
- Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism*
- Vascular Endothelial Growth Factor Receptor-2/physiology*
- PubMed
- 23575676 Full text @ Nat. Commun.
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.