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

Authors
 Hyun-Jung Choi  ;  Haiying Zhang  ;  Hongryeol Park  ;  Kyu-Sung Choi  ;  Heon-Woo Lee  ;  Vijayendra Agrawal  ;  Young-Myeong Kim  ;  Young-Guen Kwon 
Citation
 NATURE COMMUNICATIONS, Vol.6 : 6943, 2015 
Journal Title
 NATURE COMMUNICATIONS 
Issue Date
2015
MeSH
Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism* ; Angiopoietin-2/genetics ; Angiopoietin-2/metabolism* ; Animals ; Aorta ; Cell Communication ; Cloning, Molecular ; Endothelial Cells/cytology* ; Endothelial Cells/metabolism* ; Gene Expression Regulation/physiology ; Human Umbilical Vein Endothelial Cells ; Humans ; Lentivirus ; Mice ; Phosphoproteins/genetics ; Phosphoproteins/metabolism* ; RNA, Small Interfering
Abstract
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.
Full Text
http://www.nature.com/ncomms/2015/150512/ncomms7943/full/ncomms7943.html#abstract
DOI
10.1038/ncomms7943
Appears in Collections:
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Choi, Hyun-Jung(최현정) ORCID logo https://orcid.org/0000-0003-3695-3420
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140228
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