Kei Miyano
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Natural Sciences,
   Position   Assistant Professor
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 / ForeginForegin
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