{"created":"2023-07-27T06:57:11.621766+00:00","id":54271,"links":{},"metadata":{"_buckets":{"deposit":"56ac31b7-283f-44e3-a0e5-4018d8ba423f"},"_deposit":{"created_by":18,"id":"54271","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"54271"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00054271","sets":["2812:2813:2827"]},"author_link":["142"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2010-06-08","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"2002 – 2006","bibliographic_titles":[{"bibliographic_title":"平成18(2006)年度 科学研究費補助金 特定領域研究 研究成果報告書概要"},{"bibliographic_title":"2006 Fiscal Year Final Research Report Summary","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{},{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"哺乳類MAPキナーゼ(MAPK)経路の足場タンパク質は、シグナル伝達の特異性維持およびMAPKの時空間的制御に関わる因子と考えられているが、詳細については不明な点が多い。本研究課題では、我々のグループが同定した足場タンパク質JSAP1、およびそのファミリーメンバーJSAP2を中心に、細胞レベル・個体レベルでの解析を行った。\n先ず、in vitro分化系を用いたjsap1欠損マウス胚性幹細胞の解析を行い、JSAP1は心筋発生および神経発生において重要な役割を担っていることを明らかにした(JBC, 2002; BBRC, 2005)。また、JSAP1-JNKシグナル伝達系はFAK (focal adhesion kinase)と協調的に働き、細胞移動の制御に関わることを見いだした(Oncogene, 2002; JBC, 2005)。足場タンパク質JSAP1は細胞間相互作用にも関与しており、PC12h細胞では細胞接着分子N-カドヘリンを介して制御していることを見いだした(BBRC, 2007)。免疫組織化学法とin situハイブリダイゼーション法を用いて胎仔および成体マウス脳を詳細に調べ、発達過程および成体脳におけるJSAP1-JNKシグナル伝達系の重要性を強く示唆する結果を得た(JNC, 2006)。さらに、jsap1ノックアウトマウス(KO)および小脳初代培養系を用いた解析を行い、JSAP1-JNKシグナル伝達系は小脳顆粒前駆細胞の増殖プログラムを分化プログラムに変更する役割を担っていることを見いだした。一方、jsap2 KOマウスを作製・解析し、JSAP2が発生過程において重要な役割を担っていることを明らかにした。\nこれらの成果は、難治疾病の病因解明や治療にも繋がると期待されるものである。特に、主に小児の小脳に発生する髄芽腫は、小脳顆粒前駆細胞の異常増殖に起因すると考えられているが、その異常増殖はJSAP1-JNKシグナル伝達系の破綻によることが強く示唆された。このように、本研究成果は、悪性腫瘍などの発症機序に関する分子レベルでの理解に貢献するとともに、JSAP1-JNKシグナル伝達系を標的とした薬剤開発にも応用されるであろう。","subitem_description_type":"Abstract"},{"subitem_description":"Scaffold proteins of the mammalian MAP kinase (MAPK) cascades are considered having critical roles in spatio-temporal regulation of MAPK pathways by organizing their signaling components into functional modules. We are particularly interested in the functions of these scaffold proteins, mainly c-Jun NH_2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1); a scaffold protein that participates in JNK MAPK cascades, both in vitro and in vivo. Our findings are summarized as follows :\n1) We first investigated the JSAP1-null ES cells. We found that the cardiomyogenesis and neurogenesis process in JSAP1-null mutants were seriously impaired, which strongly indicated that JSAP1 plays an important role in cardiomyocyte and neural development (JBC, 2002 ; BBRC, 2005).\n2) We also demonstrated that JSAP1 regulates cell movement in cooperation with the focal adhesion kinase (Oncogene, 2002 ; JBC 2005).\n3) We further showed that JSAP1 scaffold regulates cell-cell interact ions in PC12h cells specifically in the NGF-induced signaling pathway, and does so by modulating N-cadherin (BBRC, 2007) through the knock down experiments in PC12h cells.\n4) We also studied JSAP1 and JNK expression in mouse brains. Our results obtained by in situ hybridization and immunohistochemical analyses strongly suggested that JSAP1-JNK signaling plays important roles in developing and adult mouse brains (JNC, 2006).\n5) During the development of the cerebellum, massive clonal expansion of granule cell precursors (GCPs) occurs in the outer part of the external granular layer (EGL). We have provided evidence that JSAP1 and active JNK were expressed preferentially in the post-mitotic inner EGL progenitors in the developing cerebellum. Moreover, jsapl deficiency resulted in increasing numbers of proliferating GCPs in mouse embryos. Besides, overexpression of JSAP1 in cultured GCPs led to increased numbers of NeuN-positive cells together with the activation of JNK. Together, these data strongly indicated that JSAP1 promotes the cell-cycle exit and differentiation of GCPs by modulating JNK activity in cerebellar development (in preparation).","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:14086205, 研究期間(年度):2002 – 2006","subitem_description_type":"Other"},{"subitem_description":"出典：「哺乳動物のストレス応答MAPキナーゼ経路における足場タンパク質の解析」研究成果報告書　課題番号14086205\n（KAKEN：科学研究費助成事業データベース（国立情報学研究所））\n（https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14086205/140862052006kenkyu_seika_hokoku_gaiyo/)を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学がん進展制御研究所","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00060547","subitem_identifier_reg_type":"JaLC"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/search/?kw=60200937"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/search/?kw=60200937","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14086205/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-14086205/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14086205/140862052006kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-14086205/140862052006kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_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_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-06-11"}],"displaytype":"detail","filename":"CA-PR-YOSHIOKA-K-kaken 2010-2p.pdf","filesize":[{"value":"125.3 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"CA-PR-YOSHIOKA-K-kaken 2010-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/54271/files/CA-PR-YOSHIOKA-K-kaken 2010-2p.pdf"},"version_id":"1c02bf2a-1162-483c-86c1-2e038087f28a"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"哺乳動物のストレス応答MAPキナーゼ経路における足場タンパク質の解析","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"哺乳動物のストレス応答MAPキナーゼ経路における足場タンパク質の解析"},{"subitem_title":"Functional analysis of scaffold proteins for mammalian stress-responsive MAP kinase signaling pathways","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2827"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-06-11"},"publish_date":"2021-06-11","publish_status":"0","recid":"54271","relation_version_is_last":true,"title":["哺乳動物のストレス応答MAPキナーゼ経路における足場タンパク質の解析"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:33:03.382131+00:00"}