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Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor
https://ir.soken.ac.jp/records/1124
https://ir.soken.ac.jp/records/1124edace3b8-c90c-4ccf-b643-6f3ff4a3c0d9
| 名前 / ファイル | ライセンス | アクション |
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要旨・審査要旨 / Abstract, Screening Result (208.6 kB)
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本文 (2.6 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2010-02-22 | |||||
| タイトル | ||||||
| タイトル | Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor | |||||
| タイトル | ||||||
| タイトル | Regulation of volume-sensitive chloride channels by cystic fibrosis transmembrane conductance regulator and epidermal growth factor receptor | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| 著者名 |
ABDULLAEV, Iskandar Fatkhullaevich
× ABDULLAEV, Iskandar Fatkhullaevich |
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| フリガナ |
アブデルブ, イシカンダル
× アブデルブ, イシカンダル |
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| 著者 |
ABDULLAEV, Iskandar Fatkhullaevich
× ABDULLAEV, Iskandar Fatkhullaevich |
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| 学位授与機関 | ||||||
| 学位授与機関名 | 総合研究大学院大学 | |||||
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| 学位名 | 博士（理学） | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 総研大甲第620号 | |||||
| 研究科 | ||||||
| 値 | 生命科学研究科 | |||||
| 専攻 | ||||||
| 値 | 20 生理科学専攻 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2002-03-22 | |||||
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| 値 | 2001 | |||||
| 要旨 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 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． | |||||
| 所蔵 | ||||||
| 値 | 有 | |||||
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| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
