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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳瑞華 | |
dc.contributor.author | Chun-Hau Chen | en |
dc.contributor.author | 陳俊豪 | zh_TW |
dc.date.accessioned | 2021-06-13T17:27:44Z | - |
dc.date.available | 2004-12-21 | |
dc.date.copyright | 2004-12-21 | |
dc.date.issued | 2004 | |
dc.date.submitted | 2004-11-25 | |
dc.identifier.citation | Adachi M., Fukuda M. & Nishida E. (1999) Two co-existing mechanisms for nuclear import of MAP kinase: passive diffusion of a monomer and active transport of a dimmer. EMBO J. 18, 5347-5358
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/39405 | - |
dc.description.abstract | 死亡相關蛋白激酶(Death-associated protein kinase, DAPK)是一個具有死亡區塊(death doamin)的絲胺酸�酪胺酸激酶(serine/threonine kinase),同時發現其參與干擾素-γ(interferon-γ)所引發的細胞凋亡反應(apoptosis)。後續的研究指出在多種刺激所誘發的細胞凋亡中均有DAPK參與,同時DAPK的死亡區塊能正向地調控細胞凋亡前期的反應。為了釐清那些分子藉由與DAPK的死亡區塊作用來造成細胞凋亡前期的反應,我們利用DAPK的死亡區塊為餌,以酵母菌雙雜交系統(yeast two-hybrid)來進行篩選。篩選結果發現:胞外訊息調控激酶1及2(extracellular signal-regulated kinases 1and 2, ERK 1及ERK 2)可能會和DAPK的死亡區塊作用。我們證明:無論是在試管內或是活體內反應,DAPK可以專一性地與ERK 1及ERK 2相互作用,同時這作用是藉由座落於DAPK死亡區塊內的高保留性ERK嵌合序列(consensus ERK docking sequence)所調控。更進一步地發現在DAPK的絲胺酸735(S735)位置能被ERK所磷酸化,這意味著DAPK是ERK的受質。此外,利用各式的試管內或活體內反應分析,我們發現ERK磷酸化DAPK主要是在S375的位置,然後更重要的一點是,此磷酸化的結果會藉由降低催化反應的Km值來達到增加DAPK激酸酶反應的活性。再深入地探討ERK如何調控DAPK,本論文亦證明一個反向的調控機制:即DAPK所造成ERK進入細胞核及細胞核內訊息傳導的抑制。所以,這些發現構築了一個DAPK與ERK相互調控的機轉。因為ERK造成的細胞核內訊息傳導會參與部份抑制細胞凋亡的功能(anti-apoptotic function),所以我們提出一個假說:DAPK與ERK的交互作用會構成一個正向回饋反應(a positive feedback loop),最終將促進DAPK所造成的細胞凋亡。事實上,我們的實驗數據顯示在過量表現DAPK的細胞中,ERK的活性可以促進DAPK所導致的細胞凋亡。除此之外,破壞既有的ERK與DAPK相互作用(藉由過量表現DAPK死亡區塊的方式),會降低因Fas誘發同時DAPK參與的細胞凋亡反應。最後,在生理上的細胞凋亡系統中,我們發現正向調節ERK-DAPK複合物(ERK-DAPK complex)的生成及促進其後續的雙向調控,和細胞凋亡均有高度的相關性。再者,在此系統中無論是抑制ERK的活性或是降低DAPK的表現都能有效地抑制細胞凋亡。所以提出了生理證據證明ERK-DAPK複合體能促進細胞凋亡的進行。總結而論,這些結果顯示DAPK和ERK之間的雙向訊息傳遞經由DAPK死亡區塊來促使細胞凋亡。 | zh_TW |
dc.description.abstract | Death-associated protein kinase (DAPK) is a death domain (DD)-containing serine/threonine kinase identified by its participation in the interferon- | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T17:27:44Z (GMT). No. of bitstreams: 1 ntu-93-D88448003-1.pdf: 5898669 bytes, checksum: 7769ddbb207ed9a29a896c8a83363b9a (MD5) Previous issue date: 2004 | en |
dc.description.tableofcontents | • Table of Content...................1
• Abbreviation.......................5 • 中文摘要...........................7 • Abstract...........................8 • Chapter I .........................9 • Chapter II.........................34 • References.........................104 | |
dc.language.iso | en | |
dc.title | DAPK與ERK之交互作用在促進細胞死亡訊息傳遞上
的調控分析 | zh_TW |
dc.title | Bi-directional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 呂勝春,周祖述,施修明,張智芬 | |
dc.subject.keyword | 死亡蛋白激酶,胞外訊息調控激酶, | zh_TW |
dc.subject.keyword | DAPK,ERK, | en |
dc.relation.page | 130 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2004-11-25 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
顯示於系所單位: | 分子醫學研究所 |
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