{"created":"2023-06-20T13:21:01.996586+00:00","id":1124,"links":{},"metadata":{"_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":["2:430:22"]},"author_link":["9392","9390","9391"],"item_1_creator_2":{"attribute_name":"著者名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ABDULLAEV,  Iskandar Fatkhullaevich"}],"nameIdentifiers":[{}]}]},"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":[{}]}]},"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_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．<br /><br />In 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_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ABDULLAEV,  Iskandar Fatkhullaevich","creatorNameLang":"en"}],"nameIdentifiers":[{}]}]},"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","filename":"甲620_要旨.pdf","filesize":[{"value":"208.6 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","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":"8e35fdb7-1750-40da-9be8-afaeabfbcc3c"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-02-17"}],"displaytype":"simple","filename":"甲620_本文.pdf","filesize":[{"value":"2.6 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文","url":"https://ir.soken.ac.jp/record/1124/files/甲620_本文.pdf"},"version_id":"cad3aa2b-bc60-421b-b7f1-720314fe85c6"}]},"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":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor","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"],"pubdate":{"attribute_name":"公開日","attribute_value":"2010-02-22"},"publish_date":"2010-02-22","publish_status":"0","recid":"1124","relation_version_is_last":true,"title":["Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor"],"weko_creator_id":"1","weko_shared_id":1},"updated":"2023-06-20T14:47:27.462332+00:00"}