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Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2
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Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2
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Journal Article
Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 38/77
/ 38/90
/ 96/109
/ 96/95
/ Adaptor Proteins, Signal Transducing - genetics
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Aorta
/ Endothelial Cells - cytology
/ Endothelial Cells - metabolism
/ Gene Expression Regulation - physiology
/ Human Umbilical Vein Endothelial Cells
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Phosphoproteins - metabolism
/ Science
