Kei Miyano
Department Kawasaki Medical School Kawasaki Medical School, Department of Natural Sciences, Position Assistant Professor |
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Article types | 原著 |
Language | English |
Peer review | Peer reviewed |
Title | The NADPH oxidase NOX4 promotes the directed migration of endothelial cells by stabilizing vascular endothelial growth factor receptor 2 protein |
Journal | Formal name:The Journal of Biological Chemistry Abbreviation:J Biol Chem ISSN code:1083351X |
Domestic / Foregin | Foregin |
Publisher | American Society for Biochemistry and Molecular Biology |
Total page number | 10 |
Author and coauthor | MiyanoK, Okamoto S, Yamauchi A, Kawai, C, Kajikawa M, Kiyohara T, Tamura T, Taura M, Kuribayashi F |
Authorship | Lead author,Corresponding author |
Publication date | 2020/07/02 |
Summary | 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 |
Document No. | RA120.014723 |
PMID | 32616654 |
URL for researchmap | https://www.jbc.org/content/early/2020/07/02/jbc.RA120.014723.abstract |