ミヤノ　ケイ   Kei Miyano   宮野　佳    所属   川崎医科大学  医学部 一般教養　自然科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The NADPH oxidase NOX4 promotes the directed migration of endothelial cells by stabilizing vascular endothelial growth factor receptor 2 protein
掲載誌名	正式名：The Journal of Biological Chemistry 略　 称：J Biol Chem ISSNコード：1083351X
掲載区分	国外
出版社	American Society for Biochemistry and Molecular Biology
総ページ数	10
著者・共著者	MiyanoK, Okamoto S, Yamauchi A, Kawai, C, Kajikawa M, Kiyohara T, Tamura T, Taura M, Kuribayashi F
担当区分	筆頭著者,責任著者
発行年月	2020/07/02
概要	Directed migration of endothelial cells (ECs) is an important process during both physiological and pathological angiogenesis. The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the EC surface is necessary for directed migration of these cells. Here, we used TAXIScan, an optically accessible real-time horizontal cell dynamics assay approach, and demonstrate that reactive oxygen species (ROS)-producing NADPH oxidase 4 (NOX4), which is abundantly expressed in ECs, mediates VEGF/VEGFR-2-dependent directed migration. We noted that a continuous supply of endoplasmic reticulum (ER)-retained VEGFR-2 to the plasma membrane is required to maintain VEGFR-2 at the cell surface. siRNA-mediated NOX4 silencing decreased the ER-retained form of VEGFR-2, resulting in decreased cell-surface expression levels of the receptor. We also found that ER-localized NOX4 interacts with ER-retained VEGFR-2 and thereby stabilizes this ER-retained form at the protein level in the ER. We conclude that NOX4 contributes to the directed migration of ECs by maintaining VEGFR-2 levels at their surface.
DOI	10.1074/jbc.RA120.014723
文献番号	RA120.014723
PMID	32616654
researchmap用URL	https://www.jbc.org/content/early/2020/07/02/jbc.RA120.014723.abstract