{"created":"2023-07-27T06:29:25.030261+00:00","id":14207,"links":{},"metadata":{"_buckets":{"deposit":"9b786a6e-0cc9-4555-9e75-f87ae3c468dd"},"_deposit":{"created_by":3,"id":"14207","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"14207"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00014207","sets":["1132:1133:1134"]},"author_link":["24379","258","174","21404","55"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2015-03-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"10","bibliographicPageEnd":"6105","bibliographicPageStart":"6086","bibliographicVolumeNumber":"290","bibliographic_titles":[{"bibliographic_title":"Journal of Biological Chemistry"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"We have recently demonstrated that the PI3K class II-α isoform (PI3K-C2α), which generates phosphatidylinositol 3-phosphate and phosphatidylinositol 3,4-bisphosphates, plays crucial roles in angiogenesis, by analyzing PI3K-C2α knock-out mice. The PI3K-C2α actions are mediated at least in part through its participation in the internalization of VEGF receptor-2 and sphingosine-1-phosphate receptor S1P1 and thereby their signaling on endosomes. TGFβ, which is also an essential angiogenic factor, signals via the serine/threonine kinase receptor complex to induce phosphorylation of Smad2 and Smad3 (Smad2/3). SARA (Smad anchor for receptor activation) protein, which is localized in early endosomes through its FYVE domain, is required for Smad2/3 signaling. In the present study, we showed that PI3K-C2α knockdown nearly completely abolished TGFβ1-induced phosphorylation and nuclear translocation of Smad2/3 in vascular endothelial cells (ECs). PI3K-C2α was necessary for TGFβ-induced increase in phosphatidylinositol 3,4-bisphosphates in the plasma membrane and TGFβ receptor internalization into the SARA-containing early endosomes, but not for phosphatidylinositol 3-phosphate enrichment or localization of SARA in the early endosomes. PI3K-C2α was also required for TGFβ receptor-mediated formation of SARA-Smad2/3 complex. Inhibition of dynamin, which is required for the clathrin-dependent receptor endocytosis, suppressed both TGFβ receptor internalization and Smad2/3 phosphorylation. TGFβ1 stimulated Smad-dependent VEGF-A expression, VEGF receptor-mediated EC migration, and capillary-like tube formation, which were all abolished by either PI3K-C2α knockdown or a dynamin inhibitor. Finally, TGFβ1-induced microvessel formation in Matrigel plugs was greatly attenuated in EC-specific PI3K-C2α-deleted mice. These observations indicate that PI3K-C2α plays the pivotal role in TGFβ receptor endocytosis and thereby Smad2/3 signaling, participating in angiogenic actions of TGFβ. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.","subitem_description_type":"Abstract"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Biochemistry and Molecular Biology"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1074/jbc.M114.601484","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA00251083","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0021-9258","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Aki, Sho"}],"nameIdentifiers":[{"nameIdentifier":"24379","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Yoshioka, Kazuaki"}],"nameIdentifiers":[{"nameIdentifier":"174","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"80333368","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=80333368"},{"nameIdentifier":"80333368","nameIdentifierScheme":"金沢大学研究者情報","nameIdentifierURI":"http://ridb.kanazawa-u.ac.jp/public/detail.php?kaken=80333368"},{"nameIdentifier":"80333368","nameIdentifierScheme":"研究者番号","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000080333368"}]},{"creatorNames":[{"creatorName":"Okamoto, Yasuo"}],"nameIdentifiers":[{"nameIdentifier":"258","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"80293877","nameIdentifierScheme":"研究者番号","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000080293877"}]},{"creatorNames":[{"creatorName":"Takuwa, Noriko"}],"nameIdentifiers":[{"nameIdentifier":"21404","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"70150290","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=70150290"},{"nameIdentifier":"70150290","nameIdentifierScheme":"研究者番号","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000070150290"}]},{"creatorNames":[{"creatorName":"Takuwa, Yoh"}],"nameIdentifiers":[{"nameIdentifier":"55","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"60171592","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://kaken.nii.ac.jp/ja/search/?qm=60171592"},{"nameIdentifier":"60171592","nameIdentifierScheme":"金沢大学研究者情報","nameIdentifierURI":"http://ridb.kanazawa-u.ac.jp/public/detail.php?kaken=60171592"},{"nameIdentifier":"60171592","nameIdentifierScheme":"研究者番号","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000060171592"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-03"}],"displaytype":"detail","filename":"ME-PR-TAKUWA-Y-6086.pdf","filesize":[{"value":"2.5 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ME-PR-TAKUWA-Y-6086.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/14207/files/ME-PR-TAKUWA-Y-6086.pdf"},"version_id":"ba11881a-5dd7-4315-9cf1-f7a05b3baf6e"}]},"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":"Phosphatidylinositol 3-kinase class II α-isoform PI3K-C2α is required for transforming growth factor β-induced smad signaling in endothelial cells","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Phosphatidylinositol 3-kinase class II α-isoform PI3K-C2α is required for transforming growth factor β-induced smad signaling in endothelial cells"}]},"item_type_id":"4","owner":"3","path":["1134"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-03"},"publish_date":"2017-10-03","publish_status":"0","recid":"14207","relation_version_is_last":true,"title":["Phosphatidylinositol 3-kinase class II α-isoform PI3K-C2α is required for transforming growth factor β-induced smad signaling in endothelial cells"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2024-06-20T07:04:11.053284+00:00"}