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- Title
VE-PTP controls blood vessel development by balancing Tie-2 activity.
- Authors
Winderlich, Mark; Keller, Linda; Cagna, Giuseppe; Broermann, Andre; Kamenyeva, Olena; Kiefer, Friedemann; Deutsch, Urban; Nottebaum, Astrid F; Vestweber, Dietmar
- Abstract
Vascular endothelial protein tyrosine phosphatase (VE-PTP) is an endothelial-specific receptor-type tyrosine phosphatase that associates with Tie-2 and VE-cadherin. VE-PTP gene disruption leads to embryonic lethality, vascular remodeling defects, and enlargement of vascular structures in extraembryonic tissues. We show here that antibodies against the extracellular part of VE-PTP mimic the effects of VE-PTP gene disruption exemplified by vessel enlargement in allantois explants. These effects require the presence of the angiopoietin receptor Tie-2. Analyzing the mechanism we found that anti-VE-PTP antibodies trigger endocytosis and selectively affect Tie-2-associated, but not VE-cadherin-associated VE-PTP. Dissociation of VE-PTP triggers the activation of Tie-2, leading to enhanced endothelial cell proliferation and enlargement of vascular structures through activation of Erk1/2. Importantly, the antibody effect on vessel enlargement is also observed in newborn mice. We conclude that VE-PTP is required to balance Tie-2 activity and endothelial cell proliferation, thereby controlling blood vessel development and vessel size.
- Publication
The Journal of cell biology, 2009, Vol 185, Issue 4, p657
- ISSN
1540-8140
- Publication type
Journal Article
- DOI
10.1083/jcb.200811159