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

• Published in: Nature communications Vol. 6; no. 1; p. 6943
• Main Authors: Choi, Hyun-Jung, Zhang, Haiying, Park, Hongryeol, Choi, Kyu-Sung, Lee, Heon-Woo, Agrawal, Vijayendra, Kim, Young-Myeong, Kwon, Young-Guen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.05.2015; Nature Publishing Group
• Subjects: 13/89; 14/19; 38/77; 38/90; 631/136/2060/16; 631/80/641/83/2360; 631/80/79; 631/80/79/1902; 96/109; 96/95; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Angiopoietin-2 - genetics; Angiopoietin-2 - metabolism; Animals; Aorta; Cell Communication; Cell Cycle Proteins; Cloning, Molecular; Endothelial Cells - cytology; Endothelial Cells - metabolism; Gene Expression Regulation - physiology; Human Umbilical Vein Endothelial Cells; Humanities and Social Sciences; Humans; Lentivirus; Mice; multidisciplinary; Phosphoproteins - genetics; Phosphoproteins - metabolism; RNA, Small Interfering; Science; Science (multidisciplinary); Transcription Factors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms7943

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. Angiogenesis is regulated by dynamic changes in endothelial cell contact. Here, the authors show that signals from endothelial cell junctions affect the subcellular localization and function of Yes-associated protein, ultimately modifying angiopoietin-2 expression and angiogenic activity of endothelial cells.