VE-PTP controls blood vessel development by balancing Tie-2 activity

Winderlich, Mark; Keller, Linda; Cagna, Giuseppe; Broermann, Andre; Kamenyeva, Olena; Kiefer, Friedemann; Deutsch, Urban; Nottebaum, Astrid F; Vestweber, Dietmar (2009). VE-PTP controls blood vessel development by balancing Tie-2 activity. Journal of cell biology, 185(4), pp. 657-71. New York, N.Y.: Rockefeller Institute Press 10.1083/jcb.200811159

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Deutsch, Urban

ISSN:

0021-9525

Publisher:

Rockefeller Institute Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

04 May 2014 23:23

Publisher DOI:

10.1083/jcb.200811159

PubMed ID:

19451274

Web of Science ID:

000266279900011

URI:

https://boris.unibe.ch/id/eprint/32151 (FactScience: 197079)

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