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Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells
http://hdl.handle.net/10069/32118
http://hdl.handle.net/10069/32118fc316046-f41c-46b9-8b0a-0315a49d5b32
名前 / ファイル | ライセンス | アクション |
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MBC24_1068.pdf (2.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-06-04 | |||||
タイトル | ||||||
タイトル | Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | epidermal growth factor receptor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | guanine nucleotide exchange factor | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | guanine nucleotide exchange factor h1 | |||||
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主題Scheme | Other | |||||
主題 | guanosine triphosphatase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | matrix metalloproteinase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | mitogen activated protein kinase p38 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Rac protein | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | RhoA guanine nucleotide binding protein | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | tumor necrosis factor alpha | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | tumor necrosis factor alpha converting enzyme | |||||
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主題Scheme | Other | |||||
主題 | unclassified drug | |||||
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主題Scheme | Other | |||||
主題 | animal cell | |||||
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主題Scheme | Other | |||||
主題 | article | |||||
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主題Scheme | Other | |||||
主題 | controlled study | |||||
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主題Scheme | Other | |||||
主題 | enzyme activation | |||||
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主題Scheme | Other | |||||
主題 | enzyme activity | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | enzyme phosphorylation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | epithelium | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | kidney tubule cell | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | membrane depolarization | |||||
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主題Scheme | Other | |||||
主題 | molecular dynamics | |||||
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主題Scheme | Other | |||||
主題 | nonhuman | |||||
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主題Scheme | Other | |||||
主題 | priority journal | |||||
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主題Scheme | Other | |||||
主題 | protein analysis | |||||
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主題Scheme | Other | |||||
主題 | protein cleavage | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | protein function | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | protein interaction | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | rat | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | signal transduction | |||||
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主題Scheme | Other | |||||
主題 | Western blotting | |||||
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主題Scheme | Other | |||||
主題 | wound healing | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Waheed, Faiza
× Waheed, Faiza× Dan, Qinghong× Amoozadeh, Yasaman× Zhang, Yuqian× Tanimura, Susumu× Speight, Pam× Kapus, András× Szászi, Katalin |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Transactivation of the epidermal growth factor receptor (EGFR) by tumor necrosis factor-α (TNF-α) is a key step in mediating RhoA activation and cytoskeleton and junction remodeling in the tubular epithelium. In this study we explore the mechanisms underlying TNF-α-induced EGFR activation. We show that TNF-α stimulates the TNF-α convertase enzyme (TACE/a disintegrin and metalloproteinase-17), leading to activation of the EGFR/ERK pathway. TACE activation requires the mitogen-activated protein kinase p38, which is activated through the small GTPase Rac. TNF-α stimulates both Rac and RhoA through the guanine nucleotide exchange factor (GEF)-H1 but by different mechanisms. EGFR- and ERK-dependent phosphorylation at the T678 site of GEF-H1 is a prerequisite for RhoA activation only, whereas both Rac and RhoA activation require GEF-H1 phosphorylation on S885. Of interest, GEF-H1-mediated Rac activation is upstream from the TACE/EGFR/ERK pathway and regulates T678 phosphorylation. We also show that TNF-α enhances epithelial wound healing through TACE, ERK, and GEF-H1. Taken together, our findings can explain the mechanisms leading to hierarchical activation of Rac and RhoA by TNF-α through a single GEF. This mechanism could coordinate GEF functions and fine-tune Rac and RhoA activation in epithelial cells, thereby promoting complex functions such as sheet migration. | |||||
書誌情報 |
Molecular Biology of the Cell 巻 24, 号 7, p. 1068-1082, 発行日 2013-04-01 |
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出版者 | ||||||
出版者 | American Society for Cell Biology | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 10591524 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1091/mbc.E12-09-0661 | |||||
権利 | ||||||
権利情報 | © 2013 Waheed et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Molecular Biology of the Cell, 24(7), pp.1068-1082; 2013 |