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Publication : Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2.

First Author  Choi HJ Year  2015
Journal  Nat Commun Volume  6
Pages  6943 PubMed ID  25962877
Mgi Jnum  J:224884 Mgi Id  MGI:5689239
Doi  10.1038/ncomms7943 Citation  Choi HJ, et al. (2015) Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2. Nat Commun 6:6943
abstractText  Angiogenesis is regulated by the dynamic interaction between endothelial cells (ECs). Hippo-Yes-associated protein (YAP) signalling has emerged as a key pathway that controls organ size and tissue growth by mediating cell contact inhibition. However, the role of YAP in EC has not been defined yet. Here, we show expression of YAP in the developing front of mouse retinal vessels. YAP subcellular localization, phosphorylation and activity are regulated by VE-cadherin-mediated-EC contacts. This VE-cadherin-dependent YAP phosphorylation requires phosphoinositide 3-kinase-Akt activation. We further identify angiopoietin-2 (ANG-2) as a potential transcriptional target of YAP in regulating angiogenic activity of EC in vitro and in vivo. Overexpression of YAP-active form in EC enhances angiogenic sprouting, and this effect is blocked by ANG-2 depletion or soluble Tie-2 treatment. These findings implicate YAP as a critical regulator in angiogenesis and provide new insights into the mechanism coordinating junctional stability and angiogenic activation of ECs.
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