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

Hyun-Jung Choi, Haiying Zhang, Hongryeol Park, Kyu-Sung Choi, Heon-Woo Lee, Vijayendra Agrawal, Young-Myeong Kim and Young-Guen Kwon ()
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Hyun-Jung Choi: College of Life Science and Biotechnology, Yonsei University
Haiying Zhang: College of Life Science and Biotechnology, Yonsei University
Hongryeol Park: College of Life Science and Biotechnology, Yonsei University
Kyu-Sung Choi: College of Life Science and Biotechnology, Yonsei University
Heon-Woo Lee: College of Life Science and Biotechnology, Yonsei University
Vijayendra Agrawal: College of Life Science and Biotechnology, Yonsei University
Young-Myeong Kim: School of Medicine, Kangwon National University
Young-Guen Kwon: College of Life Science and Biotechnology, Yonsei University

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7943

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