RRC ID 62924
著者 Miyano K, Okamoto S, Yamauchi A, Kawai C, Kajikawa M, Kiyohara T, Tamura M, Taura M, Kuribayashi F.
タイトル The NADPH oxidase NOX4 promotes the directed migration of endothelial cells by stabilizing vascular endothelial growth factor receptor 2 protein.
ジャーナル J Biol Chem
Abstract 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.
巻・号 295(33)
ページ 11877-11890
公開日 2020-8-14
DOI 10.1074/jbc.RA120.014723
PII S0021-9258(17)48482-1
PMID 32616654
PMC PMC7450136
MeSH Cell Line Cell Movement* Endoplasmic Reticulum / metabolism Endothelial Cells / cytology* Endothelial Cells / metabolism HeLa Cells Humans NADPH Oxidase 4 / metabolism* Protein Stability Reactive Oxygen Species / metabolism Vascular Endothelial Growth Factor Receptor-2 / metabolism*
IF 4.238
リソース情報
ヒト・動物細胞 HeLa(RCB0007)