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PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus(血小板由来増殖因子による合成型血管平滑筋細胞の遊走は、c-Srcで活性化された全長型Cav1.2 C末端を有するL型Ca2+チャネルを介する). 信州大学, 2017, 博士論文.", "subitem_description_type": "Other"}]}, "item_14_dissertation_number_7": {"attribute_name": "学位授与番号", "attribute_value_mlt": [{"subitem_dissertationnumber": "13601甲第1125号"}]}, "item_14_link_74": {"attribute_name": "WoS", "attribute_value_mlt": [{"subitem_link_text": "Web of Science", "subitem_link_url": "http://gateway.isiknowledge.com/gateway/Gateway.cgi?\u0026GWVersion=2\u0026SrcAuth=ShinshuUniv\u0026SrcApp=ShinshuUniv\u0026DestLinkType=FullRecord\u0026DestApp=WOS\u0026KeyUT=000431873800005"}]}, "item_14_publisher_4": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "信州大学"}]}, "item_14_relation_54": {"attribute_name": "PubMed", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "29441404"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://pubmed.ncbi.nlm.nih.gov/29441404/", "subitem_relation_type_select": "PMID"}}]}, "item_14_relation_55": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_name": [{"subitem_relation_name_text": "10.1007/s00424-018-2114-3"}], "subitem_relation_type_id": {"subitem_relation_type_id_text": "https://doi.org/10.1007/s00424-018-2114-3", "subitem_relation_type_select": "DOI"}}]}, "item_14_rights_69": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "The final publication is available at link.springer.com"}]}, "item_14_select_71": {"attribute_name": "著者版フラグ", "attribute_value_mlt": [{"subitem_select_item": "ETD"}]}, "item_14_text_11": {"attribute_name": "学位の区分", "attribute_value_mlt": [{"subitem_text_value": "doctoral"}]}, "item_14_text_12": {"attribute_name": "学位の分野", "attribute_value_mlt": [{"subitem_text_value": "医学"}]}, "item_14_text_13": {"attribute_name": "学位の報告番号", "attribute_value_mlt": [{"subitem_text_value": "甲第1125号"}]}, "item_14_text_76": {"attribute_name": "wosonly authkey", "attribute_value_mlt": [{"subitem_text_value": "Vascular smooth muscle cells; Platelet-derived growth factor; Ca(V)1.2 channels; c-Src"}]}, "item_14_text_77": {"attribute_name": "wosonly keywords", "attribute_value_mlt": [{"subitem_text_value": "HIGH BLOOD-PRESSURE; CALCIUM-CHANNELS; SUBUNIT; KINASE; TRANSCRIPTION; CHEMOTAXIS; MECHANISMS; ARTERIES; DOMAIN"}]}, "item_14_textarea_75": {"attribute_name": "wosonly abstract", "attribute_value_mlt": [{"subitem_textarea_value": "In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, molecular mechanism underlying the PDGF-induced migration of VSMCs remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a Ca(V)1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase (SFK)/Abl inhibitor, bosutinib, in a less-than-additive manner. PDGF significantly increased Ca(V)1.2 channel currents without altering Ca(V)1.2 protein expression levels in A7r5 cells. This reaction was inhibited by C-terminal Src kinase, a selective inhibitor of SFKs. In contractile VSMCs, the C-terminus of Ca(V)1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length Ca(V)1.2 (Ca(V)1.2FL) is expressed much more abundantly than truncated Ca(V)1.2. In a heterologous expression system, c-Src activated Ca(V)1.2 channels composed of Ca(V)1.2FL but not truncated Ca(V)1.2 (Ca(V)1.2 Delta 1763) or Ca(V)1.2 Delta 1763 plus clipped DCT. Further, c-Src enhanced the coupling efficiency between the voltage-sensing domain and activation gate of Ca(V)1.2FL channels by phosphorylating Tyr1709 and Tyr1758 in PCT. Compared with Ca(V)1.2 Delta 1763, c-Src could more efficiently bind to and phosphorylate Ca(V)1.2FL irrespective of the presence or absence of clipped DCT. 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PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus(血小板由来増殖因子による合成型血管平滑筋細胞の遊走は、c-Srcで活性化された全長型Cav1.2 C末端を有するL型Ca2+チャネルを介する)
http://hdl.handle.net/10091/00020731
http://hdl.handle.net/10091/0002073164438590-7964-4c19-8e2b-e8b2301b36f4
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内容の要旨 (123.8 kB)
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審査結果の要旨 (134.8 kB)
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博士論文の全文 (1.7 MB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2018-06-28 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus(血小板由来増殖因子による合成型血管平滑筋細胞の遊走は、c-Srcで活性化された全長型Cav1.2 C末端を有するL型Ca2+チャネルを介する) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
郭, 暁光
× 郭, 暁光 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 郭 暁光. PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus(血小板由来増殖因子による合成型血管平滑筋細胞の遊走は、c-Srcで活性化された全長型Cav1.2 C末端を有するL型Ca2+チャネルを介する). 信州大学, 2017, 博士論文. | |||||
書誌情報 |
発行日 2017-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1125号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2017-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13601 | |||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1125号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY. 470(6):909-921 (2018); doi:10.1007/s00424-018-2114-3. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://pubmed.ncbi.nlm.nih.gov/29441404/ | |||||
関連名称 | 29441404 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1007/s00424-018-2114-3 | |||||
関連名称 | 10.1007/s00424-018-2114-3 | |||||
権利 | ||||||
権利情報 | The final publication is available at link.springer.com | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000431873800005 |