{"created":"2023-07-25T10:25:34.240182+00:00","id":5968,"links":{},"metadata":{"_buckets":{"deposit":"b8b63e07-727a-4c5f-aca4-33c916f050e7"},"_deposit":{"created_by":3,"id":"5968","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"5968"},"status":"published"},"_oai":{"id":"oai:air.repo.nii.ac.jp:00005968","sets":["611:939:940"]},"author_link":["17833","17835","17840","17837","17839","17831","17834","17838","17832","17836"],"item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2018","bibliographicIssueDateType":"Issued"},"bibliographicVolumeNumber":"8","bibliographic_titles":[{"bibliographic_title":"SCIENTIFIC REPORTS"}]}]},"item_10001_description_5":{"attribute_name":"内容記述（抄録）","attribute_value_mlt":[{"subitem_description":"Pharmacological interventions to enhance fibrinolysis are effective for treating thrombotic disorders. Utilizing the in vitro U937 cell line-based fibrin degradation assay, we had previously found a cyclic pentapeptide malformin A(1) (MA(1)) as a novel activating compound for cellular fibrinolytic activity. The mechanism by which MA(1) enhances cellular fibrinolytic activity remains unknown. In the present study, we show that RSK1 is a crucial mediator of MA(1)-induced cellular fibrinolysis. Treatment with rhodamine-conjugated MA1 showed that MA(1) localizes mainly in the cytoplasm of U937 cells. Screening with an antibody macroarray revealed that MA(1) induces the phosphorylation of RSK1 at Ser380 in U937 cells. SL0101, an inhibitor of RSK, inhibited MA(1)-induced fibrinolytic activity, and CRISPR/Cas9-mediated knockout of RSK1 but not RSK2 suppressed MA1-enhanced fibrinolysis in U937 cells. Synthetic active MA(1) derivatives also induced the phosphorylation of RSK1. Furthermore, MA(1) treatment stimulated phosphorylation of ERK1/2 and MEK1/2. PD98059, an inhibitor of MEK1/2, inhibited MA(1)-induced phosphorylation of RSK1 and ERK1/2, indicating that MA1 induces the activation of the MEK-ERK-RSK pathway. Moreover, MA(1) upregulated the expression of urokinase-type plasminogen activator (uPA) and increased uPA secretion. These inductions were abrogated in RSK1 knockout cells. These results indicate that RSK1 is a key regulator of MA(1)-induced extracellular fibrinolytic activity.","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Research"}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/s41598-018-23745-0","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_25":{"attribute_name":"関連リンク","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"http://dx.doi.org/10.1038/s41598-018-23745-0"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://dx.doi.org/10.1038/s41598-018-23745-0","subitem_relation_type_select":"DOI"}}]},"item_10001_rights_15":{"attribute_name":"著作権等","attribute_value_mlt":[{"subitem_rights":"Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2018"}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"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":"Koizumi, Yukio"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nagai, Kenichiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Gao, Lina"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Koyota, Souichi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yamaguchi, Tomokazu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Natsui, Miyuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Imai, Yumiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Hasumi, Keiji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sugiyama, Toshihiro"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kuba, Keiji"}],"nameIdentifiers":[{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-02-25"}],"displaytype":"detail","filename":"iA_2022_106.pdf","filesize":[{"value":"5.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"iA_2022_106.pdf","url":"https://air.repo.nii.ac.jp/record/5968/files/iA_2022_106.pdf"},"version_id":"e69bb418-a9f6-480f-bc57-38c64712d2bd"}]},"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":"Involvement of RSK1 activation in malformin-enhanced cellular fibrinolytic activity","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Involvement of RSK1 activation in malformin-enhanced cellular fibrinolytic activity"}]},"item_type_id":"10001","owner":"3","path":["940"],"pubdate":{"attribute_name":"公開日","attribute_value":"2023-02-25"},"publish_date":"2023-02-25","publish_status":"0","recid":"5968","relation_version_is_last":true,"title":["Involvement of RSK1 activation in malformin-enhanced cellular fibrinolytic activity"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-25T10:39:03.568423+00:00"}