Jak/STAT訊息傳遞鏈中配體在果蠅發育過程扮演的角色

Tunghai University Institutional Repository > 理學院 > 生命科學系所 > 碩博士論文 > Item 310901/484

Please use this identifier to cite or link to this item: http://140.128.103.80:8080/handle/310901/484

Title:	Jak/STAT訊息傳遞鏈中配體在果蠅發育過程扮演的角色
Other Titles:	Functional study of ligands of the Jak/STAT signaling during Drosophila development
Authors:	林詩涵 Lin, Shih-Han
Contributors:	蔡玉真 Tsai, Yu-Chen 東海大學生命科學系
Keywords:	Jak/STAT 訊息傳遞鏈;Unpaired;Unpaired2;Unpaired3 Jak/STAT pathway，Unpaired，Unpaired2，Unpaired3
Date:	2010
Issue Date:	2011-01-03T06:05:40Z (UTC)
Abstract:	在哺乳動物中，Janus Kinase (Jak) /Signal Transducers and Activators of Transcription (STAT)訊息鏈受到細胞激素(cytokine)及生長因子的活化。Jak/STAT訊息鏈對於血液生成及免疫反應扮演重要的角色，若Jak/STAT訊息鏈失去調控會造成免疫疾病或癌症。哺乳動物中有四個Jaks及七個STATs，相較之下果蠅中只有一個Jak和一個STAT，具有基因不重複性及演化高度保留性。除此之外，果蠅已建立好的遺傳工具，我的研究主要是利用果蠅來研究Jak/STAT訊息鏈在發育上扮演的角色。Jak/STAT訊息鏈在果蠅參與許多發育過程，例如：胚胎體節生長、眼睛大小、血球生成、免疫反應及維持幹細胞的特性。Jak/STAT訊息鏈在果蠅中的配體 (ligand)為：Unpaired (Upd) 及兩個Unpaired-like蛋白質 (Upd2及Upd3)；兩個可能的受體 (receptor) 為：Domeless (Dome)及Domeless-like (Dome-like)。只有已是雙體的Dome及Dome-like才能夠受到Upd-like的調控，並且活化Jak/STAT訊息鏈。在胚胎、眼睛以及睪丸發育過程中，已知upd-like的基因表現位置重疊或在鄰近表達。果蠅中目前仍不清楚為何Jak/STAT這個簡單的訊息鏈 (一個Jak和STAT) 可以調控多種不同發育過程?我們推測不同配體之間及受體之間可能會形成同雙體 (homodimer) 或異雙體 (hetrodimer)，進而活化Jak/STAT訊息鏈以及不同的因子，藉由上述的反應能夠引起多種不同的發育過程。我利用共同免疫沉澱法及雙分子螢光互補技術 (Bimolecular Fluorescence Complementation technology；BiFC)，在果蠅及S2細胞株中測試不同配體間是否會形成雙體。目前，我利用共同免疫沉澱法發現Upd/Upd、Upd2/Upd2及Upd3/Upd3會形成同雙體；Upd/Upd2、Upd/Upd3及Upd2/Upd3會形成異雙體。除此之外，我利用BiFC技術發現在果蠅體內唾液腺及眼盤中，Upd/Upd、Upd2/Upd2及Upd3/Upd3會形成同雙體，Upd/Upd2、Upd2/Upd3及Upd/Upd3會形成異雙體。當在眼睛以及睪丸發育過程中，共同表達不同組合的Upd-like相較於單獨表現Upd-like蛋白質會有不同的作用。我的結果顯示，在果蠅中Upd-like蛋白質可以形成同雙體或異雙體不同多樣性組合，且不同組合的Upd-like蛋白質會影響果蠅的發育。 The Janus kinase (Jak) / Signal Transducers and Activators of Transcription (STAT) signaling transduces signals for cytokines and growth factors in mammals. The Jak/ STAT signaling plays important roles in immune responses and hematopoiesis. Mutations of this signaling cause inflammatory diseases and cancer. There are four Jaks and seven STATs in mammals. In contrast, only one Jak and one STAT exist in Drosophila. The nonredundancy of the evolutionarily conserved Jak/STAT pathway components makes Drosophila an effective animal model for studying the Jak/STAT pathway. The Jak/STAT signaling participates in multiple developmental processes, including segmentation of embryos, eye development, haematopoiesis, immune response and stem cell maintenance in Drosophila. There are three ligands, Unpaired (Upd), Upd2 and Upd3), and two putative receptors, Domeless (Dome) and Domeless-like (Dome-like) in the Drosophila Jak/STAT signaling. Only dimerized Dome receptors are competent to response Upd-like and activate the Jak/STAT pathway. The expression patterns of Unpaired-like proteins are overlapping or adjacent to each other during embryonic, eye and testis development. It is still unclear why such a simple Jak/STAT pathway (one Jak and one STAT) can mediate multiple developmental processes in Drosophila. I propose different combinations of Jak/STAT ligands and receptors can activate Jak/STAT pathway and downstream effectors. Those results induce distinct biological processes. I checked interaction of ligands in S2 cells and in vivo by co-immunoprecipitation (co-IP) and Bimolecular Fluorescence Complementation (BiFC) technology. In my preliminary data, I found that the homodimers of Upd/Upd, Upd2/Upd2 and Upd3/Upd3 and hetrodimers of Upd/Upd3, Upd/Upd3 and Upd2/Upd3 were detected by co-IP in S2 cells. Upd/Upd, Upd2/Upd2 and Upd3/Upd3 can form homodimer, Upd/Upd2, Upd/Upd3 and Upd2/Upd3 can form hetrodimers in the eye discs and salivary glands in vivo. The effects of co-expression of Upd-like are different from expression of each Upd-like protein in eye and testis. From my studies, I found Upd-like can form homodimer and hetrodimer. Different combination of Upd-like proterins can perform distinct effects in vivo.
Appears in Collections:	[生命科學系所] 碩博士論文

Files in This Item:

File	Size	Format
098THU00112012-001.pdf	3333Kb	Adobe PDF	632	View/Open

Loading...