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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 孟子青 | |
| dc.contributor.author | Abirami Santhanam | en |
| dc.contributor.author | "珊他那, 阿逼拉米" | zh_TW |
| dc.date.accessioned | 2021-05-17T09:14:54Z | - |
| dc.date.available | 2015-08-16 | |
| dc.date.available | 2021-05-17T09:14:54Z | - |
| dc.date.copyright | 2012-08-16 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-14 | |
| dc.identifier.citation | 1. Lemmon, M. A. & Schlessinger, J. (2010) Cell signaling by receptor tyrosine kinases, Cell. 141, 1117-34.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6580 | - |
| dc.description.abstract | In Drosophila, a number of cellular processes including proliferation and differentiation are regulated by protein tyrosine phosphatases (PTPs). However, to date the mechanisms by which PTPs regulate the developmental processes remain elusive especially in the case of receptor PTPs (RPTPs) which are involved in the regulation of axon guidance and synaptogenesis decisions in Drosophila embryos and larvae. To reveal the other potential functions we utilized systematic data mining approaches focusing on RPTP expression profiles during critical stages of development. This lead to the identification of a highly midgut enriched RPTP-the PTP52F especially in the larva-pupa transition during which the ecdysone action kicks in. Results from real-time PCR and cell based experiments confirmed RPTP52F as an ecdysone response gene. Genetic studies showed a critical role of PTP52F in midgut metamorphosis during larva pupa transition. Using a substrate-trapping strategy we identified, transitional endoplasmic reticulum ATPase94 (TER94), ortholog of human Valosin Containing Protein (VCP) as a bonafide substrate of PTP52F. Interestingly, tyrosine 800 of TER94 which is phosphorylated by Src kinase is targeted and dephosphorylated by PTP52F. We showed that PTP52F mediated dephosphorylation of TER94 could facilitate the ubiquitin mediated degradation of various proteins including Drosophila inhibitor of apoptosis1 (DIAP1) a key regulator controlling midgut cell death. In vivo evidences demonstrated that the forced expression of TER94 rescued the defect of midgut metamorphosis induced by knockdown of PTP52F, suggesting the importance of coordinated action between PTP52F and TER94. Our studies for the first time reveal a novel regulatory role of a RPTP that contributes to proper tissue organization of midgut formation in Drosophila metamorphosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-17T09:14:54Z (GMT). No. of bitstreams: 1 ntu-101-D95B46014-1.pdf: 3718115 bytes, checksum: ce6453496bbbebede9d62449dd8e1edc (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | TABLE OF CONTENTS
ABSTRACT………………………………………………………………………….......i ABBREVIATION……………………………………………………………………….ii TABLE OF CONTENTS……………………………………………………………….iii CHAPTER 1: INTRODUCTION....................................1 1.1 Protein tyrosine phosphatases..........................2 1.2 Substrate identification and functional characterization of PTPs....................................................3 1.3 Drosophila PTPome......................................5 1.4 Drosophila RPTP and CNS development....................6 1.5 Ligands and substrates of Drosophila RPTPs.............7 1.6 Goals of the current study.............................8 CHAPTER 2: MATERIALS AND METHODS..........................10 2.1 Fly stocks............................................11 2.2 In-gel phosphatase activity assay.....................11 2.3 Microarray and Next generation sequencing (NGS) data mining....................................................12 2.4 Generation of PTP52F antibody.........................12 2.5 Cloning and expression of PTP52F, TER94, Src42a and DIAP1.....................................................12 2.6 Cell Culture, Transfection, Immunoprecipitation and immunoblotting............................................13 2.7 Phosphatase activity assay............................14 2.8 Extraction of RNA, cDNA Synthesis and RT-PCR..........14 2.9 Quantitative Real-Time PCR............................15 2.10 Mass spectrometry based substrate trapping...........16 2.11 In vivo substrate trapping from fly tissue...........17 2.12 Immunofluorescence staining..........................17 2.13 Light Microscopy.....................................18 2.14 TUNEL staining.......................................18 CHAPTER 3: RESULTS AND DISCUSSION.........................19 3.1 Profiling of PTPs during Drosophila development by in-gel phosphatase activity assay............................20 3.2 Data mining from modENCODE to depict the mRNA expression profiles of RPTPs during Drosophila development...............................................21 3.3 Tissue distribution of RPTPs during third instar larval stage.....................................................22 3.4 PTP52F is highly enriched in midgut during larva-pupa transition................................................23 3.5 PTP52F is an ecdysone response gene...................24 3.6 PTP52F mutants shows delay in midgut metamorphosis...25 3.7 Ectopically expressed PTP52F is an active, plasma membrane-localized phosphatase............................26 3.8 VCP/TER94 is a potential substrate of PTP52F and is also involved in midgut metamorphosis..........................27 3.9 Src42A is the upstream kinase of TER94................30 3.10 Src42A may not be the substrate of PTP52F............30 3.11 PTP52F dephosphorylates TER94 Tyr(Y)-800 under ecdysone ..........................................................31 3.12 TER94 tyrosine phosphorylation regulates its function in degradation of ubiquitinated substrates................32 3.13 TER94-dependent degradation of the apoptosis inhibitor DIAP1 is regulated by TER94 phosphorylation status........34 3.14 Delay in midgut metamorphosis is due to reduced cell death revealed by TUNEL staining..........................35 3.15 Summary..............................................36 3.16 Discussion...........................................37 CHAPTER 4: FUTURE STUDIES.................................40 4.1 Future directions.....................................41 CHAPTER 5: FIGURES........................................44 CHAPTER 6: REFERENCES.....................................72 APPENDIX-I................................................82 APPENDIX-II..............................................102 | |
| dc.language.iso | en | |
| dc.title | 酪氨酸磷酸水解酶PTP52F對於果蠅發育之重要性 | zh_TW |
| dc.title | Role of the midgut-enriched receptor protein tyrosine phosphatase PTP52F in Drosophila melanogaster | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 陳光超 | |
| dc.contributor.oralexamcommittee | 張震東,邱繼輝,陳俊宏,桑自剛 | |
| dc.subject.keyword | PTP52F,果蠅,發育, | zh_TW |
| dc.subject.keyword | Drosophila,Development,Midgut,PTP52F,metamorphosis, | en |
| dc.relation.page | 115 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2012-08-14 | |
| 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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| ntu-101-1.pdf | 3.63 MB | Adobe PDF | 檢視/開啟 |
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