本文關(guān)鍵詞： Vangl2 Scrib1 WNT NTDs PTPN18 酵母雙雜交 信號(hào)轉(zhuǎn)導(dǎo)　出處：《蘭州大學(xué)》2006年碩士論文　論文類型：學(xué)位論文

【摘要】：Vangl2為高度保守的膜蛋白,它是一個(gè)521個(gè)氨基酸的跨膜蛋白,N-端有四個(gè)跨膜結(jié)構(gòu)域,C-端在細(xì)胞質(zhì)面,含有一個(gè)PDZ結(jié)合結(jié)構(gòu)域,與細(xì)胞內(nèi)信號(hào)轉(zhuǎn)導(dǎo)或與細(xì)胞內(nèi)其他信號(hào)分子相互作用有關(guān)。Vangl2是一個(gè)非經(jīng)典WNT信號(hào)通路的一種成分,與細(xì)胞平面極化(PCR,planar cell polarity)相關(guān),調(diào)節(jié)細(xì)胞排布的方向,Vangl2突變導(dǎo)致小鼠產(chǎn)生looped-tail表型,這種小鼠有神經(jīng)管閉合缺陷。 Scrib1為一種抑癌基因,文獻(xiàn)報(bào)道,用果蠅胚胎上皮細(xì)胞、卵泡上皮細(xì)胞、視盤上皮細(xì)胞為研究對(duì)象,發(fā)現(xiàn)Scrib1突變導(dǎo)致上皮組織極化失常,失去上皮細(xì)胞的正常結(jié)構(gòu),使其過(guò)度生長(zhǎng)。Scrib1插入突變使小鼠產(chǎn)生Circletail(Crc)表型,與Vangl2突變一樣,這種小鼠也有神經(jīng)管閉合缺陷,同時(shí)越來(lái)越多的文獻(xiàn)報(bào)道Scrib1也參與PCP信號(hào)過(guò)程,與Scrib1相關(guān)的分子也與Vangl2存在直接或者間接的相互聯(lián)系,提示它們?cè)谛盘?hào)通路上存在交叉。 本文主要研究Vangl2與Scrib1的相互作用,用pull-down證明Scrib1和Vangl2存在相互作用,并采用了酵母雙雜交技術(shù)研究Vangl2的信號(hào)途徑,我們選擇構(gòu)建編碼Vangl2的C-末端的基因片段為酵母雙雜交的誘餌(bait),篩選胎腦庫(kù)得到了一些候選基因,其中一個(gè)為非受體類型蛋白酪氨酸磷酸酯酶(protein tyrosine phosphatase non-receptor)PTPN18。酪氨酸激酶對(duì)原癌基因的激活在癌細(xì)胞信號(hào)轉(zhuǎn)導(dǎo)中是很普遍的一種現(xiàn)象,酪氨酸磷酸化也由蛋白酪氨酸磷酸酯酶/酪氨酸激酶控制,一些蛋白酪氨酸磷酸酯酶含有SHP2結(jié)構(gòu)域,能正向調(diào)節(jié)生長(zhǎng)因子受體的信號(hào)通路,具有致癌性。 在WNT信號(hào)通路中:WNT活化Fz信號(hào),Fz磷酸化Dsh,Dsh抑制GSK-3β,使β-catenin累積,調(diào)節(jié)各種基因轉(zhuǎn)錄,β-catenin的磷酸化和去磷酸化對(duì)于信號(hào)通路有著重要的作用。我們注意到Vangl2與Fz受體一樣也是一個(gè)膜蛋白,而它與PTPN18這個(gè)酪氨酸磷酸酯酶存在相互作用,同時(shí)本實(shí)驗(yàn)室以前用酵母雙雜證明Scrib1和proline-serine-threonine phosphatase interacting protein 1(pstpip 1)蛋白相互作用,而通過(guò)www.bind.ac數(shù)據(jù)庫(kù),查到pstpip1和ptpn18有相互作用,我們有理由認(rèn)為這個(gè)Vangl2膜受體受到細(xì)胞外分子信號(hào)的刺激后,至少形成Vangl2-ptpn18-pstpip1-Scrib1的復(fù)合體,使某個(gè)下游分子或者蛋白復(fù)合體中的某個(gè)成分磷酸/去磷酸化,導(dǎo)致一系列的效應(yīng)。
[Abstract]:Vangl2 is a highly conserved membrane protein. It is a 521 amino acid transmembrane protein with four transmembrane domains C- terminal in the cytoplasm and a PDZ binding domain. Vangl2 is a component of a nonclassical WNT signaling pathway associated with intracellular signal transduction or interaction with other intracellular signaling molecules. Planar cell polarity). The mutation of Vangl2, which regulates the distribution of cells, leads to the production of looped-tail phenotype in mice. This mouse has a neural tube closure defect. Scrib1 is a tumor suppressor gene. The embryonic epithelial cells, follicular epithelial cells and optic disk epithelial cells of Drosophila melanogaster were used in this study. It was found that Scrib1 mutation resulted in abnormal polarization of epithelial tissue and loss of normal structure of epithelial cells. The insertion mutation of Scrib1 caused the mice to produce Circletaila Crcc phenotype, which, like the Vangl2 mutation, had neural tube closure defects. At the same time, more and more literatures have reported that Scrib1 is also involved in the PCP signal process, and Scrib1 related molecules are directly or indirectly related to Vangl2. These results suggest that they are intersected in signal pathway. In this paper, the interaction between Vangl2 and Scrib1 is studied, and the existence of interaction between Scrib1 and Vangl2 is proved by pull-down. Yeast two-hybrid technique was used to study the signal pathway of Vangl2. We selected the C-terminal gene fragment encoding Vangl2 as the bait of yeast two-hybrid. A number of candidate genes were obtained from the screening of fetal brain banks, one of which was a non-receptor type protein tyrosine phosphatase protein. Tyrosine phosphatase non-receptor). PTPN18. the activation of proto-oncogene by tyrosine kinase is a common phenomenon in cancer cell signal transduction. Tyrosine phosphorylation is also controlled by protein tyrosine phosphatase / tyrosine kinase. Some protein tyrosine phosphatase contain SHP2 domain and can positively regulate the signal pathway of growth factor receptor. Carcinogenic. In the WNT signaling pathway, WNT activates FZ phosphorylation of GSK-3 尾, inhibits the accumulation of 尾 -catenin, and regulates the transcription of various genes. The phosphorylation and dephosphorylation of 尾 -catenin play an important role in the signaling pathway. We note that Vangl2 is a membrane protein as well as FZ receptor. And it interacts with PTPN18, a tyrosine phosphatase. At the same time, we used yeast double hybrid to prove Scrib1 and proline-serine-threonine phosphatase. Interacting protein 1. Pstpip 1) protein interaction. Through the www.bind.ac database, the interaction between pstpip1 and ptpn18 was found. It is reasonable to believe that this Vangl2 membrane receptor is stimulated by extracellular molecular signals and at least forms a complex of Vangl2-ptpn18-pstpip1-Scrib1. Phosphorylation of a component of a downstream molecule or protein complex leads to a series of effects.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R341;Q78

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