{"created":"2023-05-15T16:34:36.520142+00:00","id":7276,"links":{},"metadata":{"_buckets":{"deposit":"5b282318-09ce-4faa-afb0-58c751c05b08"},"_deposit":{"created_by":2,"id":"7276","owners":[2],"pid":{"revision_id":0,"type":"depid","value":"7276"},"status":"published"},"_oai":{"id":"oai:nagasaki-u.repo.nii.ac.jp:00007276","sets":["73:74"]},"author_link":["30535","30536","30532","30534","30537","30530","30533","30531"],"item_2_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013-04-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"7","bibliographicPageEnd":"1082","bibliographicPageStart":"1068","bibliographicVolumeNumber":"24","bibliographic_titles":[{"bibliographic_title":"Molecular Biology of the Cell"}]}]},"item_2_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_type":"Abstract"}]},"item_2_description_63":{"attribute_name":"引用","attribute_value_mlt":[{"subitem_description":"Molecular Biology of the Cell, 24(7), pp.1068-1082; 2013","subitem_description_type":"Other"}]},"item_2_publisher_33":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Cell Biology"}]},"item_2_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1091/mbc.E12-09-0661","subitem_relation_type_select":"DOI"}}]},"item_2_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 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)."}]},"item_2_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"10591524","subitem_source_identifier_type":"ISSN"}]},"item_2_version_type_16":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Waheed, Faiza"}],"nameIdentifiers":[{"nameIdentifier":"30530","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Dan, Qinghong"}],"nameIdentifiers":[{"nameIdentifier":"30531","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Amoozadeh, Yasaman"}],"nameIdentifiers":[{"nameIdentifier":"30532","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yuqian"}],"nameIdentifiers":[{"nameIdentifier":"30533","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Tanimura, Susumu"}],"nameIdentifiers":[{"nameIdentifier":"30534","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Speight, Pam"}],"nameIdentifiers":[{"nameIdentifier":"30535","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kapus, András"}],"nameIdentifiers":[{"nameIdentifier":"30536","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Szászi, Katalin"}],"nameIdentifiers":[{"nameIdentifier":"30537","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-12-21"}],"displaytype":"detail","filename":"MBC24_1068.pdf","filesize":[{"value":"2.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"MBC24_1068.pdf","url":"https://nagasaki-u.repo.nii.ac.jp/record/7276/files/MBC24_1068.pdf"},"version_id":"3bb10343-3b85-4be0-9441-792eb9a37983"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"epidermal growth factor receptor","subitem_subject_scheme":"Other"},{"subitem_subject":"guanine nucleotide exchange factor","subitem_subject_scheme":"Other"},{"subitem_subject":"guanine nucleotide exchange factor h1","subitem_subject_scheme":"Other"},{"subitem_subject":"guanosine triphosphatase","subitem_subject_scheme":"Other"},{"subitem_subject":"matrix metalloproteinase","subitem_subject_scheme":"Other"},{"subitem_subject":"mitogen activated protein kinase p38","subitem_subject_scheme":"Other"},{"subitem_subject":"Rac protein","subitem_subject_scheme":"Other"},{"subitem_subject":"RhoA guanine nucleotide binding protein","subitem_subject_scheme":"Other"},{"subitem_subject":"tumor necrosis factor alpha","subitem_subject_scheme":"Other"},{"subitem_subject":"tumor necrosis factor alpha converting enzyme","subitem_subject_scheme":"Other"},{"subitem_subject":"unclassified drug","subitem_subject_scheme":"Other"},{"subitem_subject":"animal cell","subitem_subject_scheme":"Other"},{"subitem_subject":"article","subitem_subject_scheme":"Other"},{"subitem_subject":"controlled study","subitem_subject_scheme":"Other"},{"subitem_subject":"enzyme activation","subitem_subject_scheme":"Other"},{"subitem_subject":"enzyme activity","subitem_subject_scheme":"Other"},{"subitem_subject":"enzyme phosphorylation","subitem_subject_scheme":"Other"},{"subitem_subject":"epithelium","subitem_subject_scheme":"Other"},{"subitem_subject":"kidney tubule cell","subitem_subject_scheme":"Other"},{"subitem_subject":"membrane depolarization","subitem_subject_scheme":"Other"},{"subitem_subject":"molecular dynamics","subitem_subject_scheme":"Other"},{"subitem_subject":"nonhuman","subitem_subject_scheme":"Other"},{"subitem_subject":"priority journal","subitem_subject_scheme":"Other"},{"subitem_subject":"protein analysis","subitem_subject_scheme":"Other"},{"subitem_subject":"protein cleavage","subitem_subject_scheme":"Other"},{"subitem_subject":"protein function","subitem_subject_scheme":"Other"},{"subitem_subject":"protein interaction","subitem_subject_scheme":"Other"},{"subitem_subject":"rat","subitem_subject_scheme":"Other"},{"subitem_subject":"signal transduction","subitem_subject_scheme":"Other"},{"subitem_subject":"Western blotting","subitem_subject_scheme":"Other"},{"subitem_subject":"wound healing","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells"}]},"item_type_id":"2","owner":"2","path":["74"],"pubdate":{"attribute_name":"公開日","attribute_value":"2013-06-04"},"publish_date":"2013-06-04","publish_status":"0","recid":"7276","relation_version_is_last":true,"title":["Central role of the exchange factor GEF-H1 in TNF-α–induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells"],"weko_creator_id":"2","weko_shared_id":-1},"updated":"2023-05-16T02:27:53.776309+00:00"}