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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳瑞華 | |
| dc.contributor.author | Ching-Jung Lin | en |
| dc.contributor.author | 林靖容 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:52:02Z | - |
| dc.date.available | 2015-08-12 | |
| dc.date.copyright | 2010-08-12 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-02 | |
| dc.identifier.citation | Abramoff, M.D., Magelhaes, P.J., Ram, S.J. (2004). Image Processing with ImageJ. Biophotonics International 11, 36-42.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/46038 | - |
| dc.description.abstract | 乳癌激酶(Breast tumor kinase, B3rk)是一種與Src有高度相似性的非受體型酪
胺酸激酶， 已有多篇文獻指出在乳癌和多種癌症中可偵測到乳癌激酶的高量表 現。據本實驗室過去的研究，我們發現乳癌激酶可磷酸化paxillin和p190RhoGAPA 這兩個受質，進一步促進Rac1的活化和細胞移動。本篇論文中，我們將探討一 個新的乳癌激酶交互作用因子與受質，表皮生長因子受器受質八(epidermal growth factor receptor pathway substrates 8, EPS8)。我們確認了此蛋白質上的第 454、485、491、498、525、723、774個酪胺酸為重要的磷酸化位置。此外，我 們意外發現EPS8受乳癌激酶磷酸化後，在細胞的附著、延展和移動的能力上扮演 抑制的角色。同時我們也觀察到Rac1活性下降，細胞應激纖維(Stress fiber)數量 上升等現象的伴隨發生。綜合以上，這些結果暗示了EPS8的磷酸化增加了 其促進激動蛋白絲結合成束狀的能力或減低了它與Abi1、SOS1等蛋白質結 合的能力，而無法形成促進Rac1活化的鳥糞嘌呤核甘酸交換因子聚合物。 我們的研究同時也揭露了乳癌激酶可藉由與不同受質交互作用，在Rac1活 化上具有刺激和抑制兩種調控功能。同時也暗示乳癌激酶對細胞移動的影 響有時間、空間條件下的特異性。 | zh_TW |
| dc.description.abstract | Breast tumor kinase (Brk), an Src-like nonreceptor tyrosine kinase, is
overexpressed in breast cancer and several other cancer types. Previous studies in our lab indicate that Brk promotes Rac activation and cell migration by phosphorylating paxillin and p190RhoGAP-A. In this thesis, we report epidermal growth factor receptor pathway substrates 8 (EPS8) as a new interacting partner and substrate of Brk. In addition, we identified seven tyrosine residues, i.e., Y454, Y485, Y491, Y498, Y525, Y723, Y774, as major sites targeted by Brk. Surprisingly, this Brk-induced EPS8 tyrosine phosphorylation plays inhibitory roles in cell adhesion, spreading and migration. These effects correlate with a downregulation of Rac1 activity and upregulation of actin stress fiber formation. Thus, our findings suggest that EPS8 tyrosine phosphorylation promotes its actin bundling activity or downregulates the formation of EPS8-Abi1-SOS1 complex, which processes a GEF activity toward Rac. Our study also reveals that Brk can elicit both inhibitory and stimulatory effects on Rac activity, via distinct downstream effectors. Such feature of Brk might facilitate a temporally or spatially specific regulation on cell migration. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:52:02Z (GMT). No. of bitstreams: 1 ntu-99-R97b46015-1.pdf: 15716825 bytes, checksum: d8ff009db8e865d76f77f3245728cb98 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | Table of Contents
口試委員會審定書..............................................................................................i 誌謝...................................................................................................................ii 中文摘要………………….......………………………………………………………...…...iii Abstract……………………….......…………………………………………………...……iv Introduction………………………......……………………………………………..……...1 1.Tumor progression…………………....………………………………..………….......1 1.1 Protein tyrosine kinase……………….........………………………………..………2 1.2 RhoGTPase and Cell Migration…………….........…………………………………4 2. Breast Tumor Kinase (Brk)……………………………......…………………………..5 2.1 Structure of Brk……………………………………………...........………………….5 2.2 Expression Pattern of Brk…………………………………………........…………..6 2.3 Brk signaling pathways…………………………………………………….........….7 3. Epidermal Growth Factor Receptor Pathway Substrate 8 (EPS8)………….....10 3.1 Structure of EPS8……………………………………………………………...........11 3.2 Expression pattern of EPS8………………………………………………….........11 3.3 Biological Functions of EPS8………………………………………………..........12 Materials and Methods………………………………………………………………......14 Results………………………………………………………………………………….......18 Discussion……………………………………………………………………………........25 Reference………………………………………………………………………….............29 Figure...........................................................................................................43 Appendix.....................................................................................................56 | |
| dc.language.iso | en | |
| dc.title | 探討乳癌激酶對表皮生長因子受器受質八磷酸化之功能調控 | zh_TW |
| dc.title | Functional Study of Brk-mediated EPS8 Phosphorylation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李明亭,陳光超 | |
| dc.subject.keyword | 乳癌激酶,表皮生長因子受器受質八,酪胺酸磷酸化,Rac,細胞移動, | zh_TW |
| dc.subject.keyword | Brk,EPS8,tyrosine phosphorylation,Rac,migration, | en |
| dc.relation.page | 56 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-08-02 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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