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) |