{"_buckets": {"deposit": "baaab691-2a60-42b7-99f0-417ace00d6d9"}, "_deposit": {"created_by": 1, "id": "1124", "owners": [1], "pid": {"revision_id": 0, "type": "depid", "value": "1124"}, "status": "published"}, "_oai": {"id": "oai:ir.soken.ac.jp:00001124", "sets": ["22"]}, "author_link": ["9392", "9390", "9391"], "item_1_biblio_info_21": {"attribute_name": "書誌情報（ソート用）", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2002-03-22", "bibliographicIssueDateType": "Issued"}, "bibliographic_titles": [{}]}]}, "item_1_creator_2": {"attribute_name": "著者名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "ABDULLAEV,  Iskandar Fatkhullaevich"}], "nameIdentifiers": [{"nameIdentifier": "9390", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_creator_3": {"attribute_name": "フリガナ", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "アブデルブ, イシカンダル"}], "nameIdentifiers": [{"nameIdentifier": "9391", "nameIdentifierScheme": "WEKO"}]}]}, "item_1_date_granted_11": {"attribute_name": "学位授与年月日", "attribute_value_mlt": [{"subitem_dategranted": "2002-03-22"}]}, "item_1_degree_grantor_5": {"attribute_name": "学位授与機関", "attribute_value_mlt": [{"subitem_degreegrantor": [{"subitem_degreegrantor_name": "総合研究大学院大学"}]}]}, "item_1_degree_name_6": {"attribute_name": "学位名", "attribute_value_mlt": [{"subitem_degreename": "博士（理学）"}]}, "item_1_description_1": {"attribute_name": "ID", "attribute_value_mlt": [{"subitem_description": "2002058", "subitem_description_type": "Other"}]}, "item_1_description_12": {"attribute_name": "要旨", "attribute_value_mlt": [{"subitem_description": "Effectene-mediated transient expression of wild-type (WT) human cystic fibrosis transmembrane conductance regulator (CFTR) in HEK293T cells resulted in a 3- times decrease of the amplitude of steady-state volume-sensitive outwardly rectifying (VSOR) chloride current, Expression of the CFTR ΔF508 mutant, which cannot be translocated to the plasma membrane， failed to mimic the CFTR effect on the VSOR Cl- current, suggesting that plasma membrane expression of CFTR protein is necessary for its regulatory effect on the VSOR Cl- channel. Expression of the G1349D mutant of CFTR, which impairs ATP binding to the NBD2 domain of CFTR protein， failed to inhibit VSOR Cl- currents．D1370N and K1250M mutations in NBD2 domain, which impair ATP hydrolysis， were also ineffective in down-regulating VSOR C1-currents．In contrast, expression of G551D mutant， which impairs ATP binding to the NBDl domain， mimicked the effect of WT- CFTR．Thus， I conclude that plasma membrane expression of an ATP- hydrolysable conformation of the NBD2 domain of CFTR is essential for its down-regulatory action on the volume-sensitive chloride conductance in HEK293T/CFTR cells．\u003cbr /\u003e\u003cbr /\u003eIn mouse mammary gland C127 cells， in contrast, VSOR Cl- currents were up- regulated by stable expression of CFTR mediated by bovine papillomavirus （BPV)， a carrier for CFTR gene transfection， by around 3-fold．Also， BPV- mediated expression with CFTR ΔF508 mutant produced a similar up-regulating effect on VSOR Cl- currents．BPV expression is known to constitutively activate receptors to platelet-derived growth factor (PDGF) and epidermal growth factor （EGF)．Application of a PDGF peptide or a specific inhibitor of PDGF tyrosine kinase， tyrphostin AGl296， had no effect on VSOR Cl-currents．In contrast， application of an EGF peptide enhanced VSOR Cl-currents in Cl27 cells, but not in Cl27 cells treated with BPV(Cl27/BPV cells)．A specific inhibitor of EGF- receptor tyrosine kinase， tyrphostin B46， profoundly suppressed VSOR Cl-currents in Cl27 and Cl27/BPV cells．Thus， I conclude that VSOR Cl-channels are enhanced by an EGF receptor tyrosine kinase signaling and that BPV-induced up-regulation overrides CFTR-induced down-regulation of VSOR Cl-channels in Cl27/CFTR cells．Since inhibitors of phospholipase Cγ(PLCγ)， phosphatidylinositol-3-kinase (PI3K) and MAP kinase kinase (MEK) failed to affect the VSOR Cl-channel activity， it might be possible that the VSOR Cl- channel is regulated by some signaling pathway, other than those involving PLCγ，PI3K and MEK, which is downstream to the EGF receptor tyrosine kinase．", "subitem_description_type": "Other"}]}, "item_1_description_18": {"attribute_name": "フォーマット", "attribute_value_mlt": [{"subitem_description": "application/pdf", "subitem_description_type": "Other"}]}, "item_1_description_7": {"attribute_name": "学位記番号", "attribute_value_mlt": [{"subitem_description": "総研大甲第620号", "subitem_description_type": "Other"}]}, "item_1_select_14": {"attribute_name": "所蔵", "attribute_value_mlt": [{"subitem_select_item": "有"}]}, "item_1_select_8": {"attribute_name": "研究科", "attribute_value_mlt": [{"subitem_select_item": "生命科学研究科"}]}, "item_1_select_9": {"attribute_name": "専攻", "attribute_value_mlt": [{"subitem_select_item": "20 生理科学専攻"}]}, "item_1_text_10": {"attribute_name": "学位授与年度", "attribute_value_mlt": [{"subitem_text_value": "2001"}]}, "item_1_text_20": {"attribute_name": "業務メモ", "attribute_value_mlt": [{"subitem_text_value": "（2018年2月16日）本籍など個人情報の記載がある旧要旨・審査要旨を個人情報のない新しいものに差し替えた。承諾書等未確認。要確認該当項目修正のこと。"}]}, "item_creator": {"attribute_name": "著者", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "ABDULLAEV,  Iskandar Fatkhullaevich", "creatorNameLang": "en"}], "nameIdentifiers": [{"nameIdentifier": "9392", "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": "2016-02-17"}], "displaytype": "simple", "download_preview_message": "", "file_order": 0, "filename": "甲620_要旨.pdf", "filesize": [{"value": "208.6 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_11", "mimetype": "application/pdf", "size": 208600.0, "url": {"label": "要旨・審査要旨 / Abstract, Screening Result", "url": "https://ir.soken.ac.jp/record/1124/files/甲620_要旨.pdf"}, "version_id": 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"item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor"}, {"subitem_title": "Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor", "subitem_title_language": "en"}]}, "item_type_id": "1", "owner": "1", "path": ["22"], "permalink_uri": "https://ir.soken.ac.jp/records/1124", "pubdate": {"attribute_name": "公開日", "attribute_value": "2010-02-22"}, "publish_date": "2010-02-22", "publish_status": "0", "recid": "1124", "relation": {}, "relation_version_is_last": true, "title": ["Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor"], "weko_shared_id": 1}