title: Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2.
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.
authors.affiliation: 1] Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea [2] Severance Integrative Research Institute for Cerebral and Cardiovascular Diseases, College of Medicine, Yonsei University, Seoul 120-752, Republic of Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Hongryeol
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Kyu-Sung
authors.initials: KS
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Heon-Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Vijayendra
authors.initials: V
authors.lastname: Agrawal
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D002450:Cell Communication; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D016086:Lentivirus; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D042702:Angiopoietin-2; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse