本文選題：Rap2　切入點(diǎn)：JNK　出處：《哈爾濱工業(yè)大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： Rap2屬于Ras家族小分子量GTP結(jié)合蛋白家族成員之一,調(diào)節(jié)細(xì)胞的增殖、粘附、遷移、侵襲等。Rap2的功能通過其下游信號(hào)分子傳遞如MAP4K4,TNIK,Raf,PARG是最近發(fā)現(xiàn)的Rap2特異效應(yīng)因子。其中MAP4K4屬于STE激酶家族成員,在多種癌細(xì)胞系中促進(jìn)細(xì)胞的遷移運(yùn)動(dòng)。而JNK作為MAP4K4,TNIK的下游效應(yīng)因子,參與細(xì)胞的運(yùn)動(dòng),凋亡等。在靜息狀態(tài)下,JNK大多以非活性的形式存在于細(xì)胞質(zhì)中,一旦被激活則轉(zhuǎn)移至細(xì)胞核或細(xì)胞膜調(diào)控細(xì)胞的凋亡及運(yùn)動(dòng)等。但JNK是否作為Rap2的下游效應(yīng)因子調(diào)控細(xì)胞的遷移運(yùn)動(dòng)還未知。 本文通過檢測Rap2對(duì)JNK表達(dá)及活性的影響及過表達(dá)Rap2對(duì)JNK在細(xì)胞內(nèi)分布的影響來初步探討Rap2-JNK信號(hào)通路在細(xì)胞遷移中的信號(hào)途徑。我們發(fā)現(xiàn)穩(wěn)定表達(dá)Rap2的HEK293細(xì)胞中,發(fā)生酪氨酸磷酸化的JNK水平較對(duì)照組明顯升高。同時(shí)發(fā)現(xiàn)過表達(dá)Rap2-12V(Rap2的活性突變體)的細(xì)胞中JNK2的表達(dá)降低。另外,利用免疫熒光技術(shù)發(fā)現(xiàn)過表達(dá)Rap2的NIH3T3中JNK較對(duì)照組相比具有細(xì)胞核內(nèi)聚集傾向,進(jìn)一步提示Rap2對(duì)JNK的活化作用。在細(xì)胞遷移實(shí)驗(yàn)中,過表達(dá)Rap2的Caki-1細(xì)胞較對(duì)照組遷移速度明顯加快,而加入JNK抑制劑SP600125能抑制Rap2誘導(dǎo)的細(xì)胞遷移�？偵纤�,我們的實(shí)驗(yàn)結(jié)果初步表明Rap2通過對(duì)JNK活性和細(xì)胞定位的調(diào)控調(diào)節(jié)細(xì)胞的遷移。
[Abstract]:Rap2 is a member of small molecular weight GTP binding protein family of Ras family, which regulates cell proliferation, adhesion and migration. The function of Rap2 is transmitted through its downstream signaling molecules, such as MAP4K4, TNIKPERG, a recently discovered Rap2 specific effector, in which MAP4K4 is a member of the STE kinase family. JNK, as a downstream effector of MAP4K4tTNIK, participates in cell movement, apoptosis and so on. In resting state, JNK exists in cytoplasm in the form of inactivity. Once activated, it was transferred to the nucleus or cell membrane to regulate the apoptosis and movement of cells, but it is not known whether JNK acts as a downstream effector of Rap2 to regulate the migration of cells. The effect of Rap2 on the expression and activity of JNK and the effect of overexpression of Rap2 on the distribution of JNK in cells were studied to explore the signal pathway of Rap2-JNK signaling pathway in cell migration. We found that the expression of Rap2 was stable in HEK293 cells. The level of JNK with tyrosine phosphorylation was significantly higher than that of control group. At the same time, the expression of JNK2 was decreased in the active mutants that expressed Rap2-12V(Rap2. It was found by immunofluorescence technique that JNK in NIH3T3, which was overexpressed by Rap2, had a tendency of aggregation in nucleus compared with that in control group, which further indicated the activation of JNK by Rap2. The migration rate of Caki-1 cells with overexpression of Rap2 was significantly faster than that of control group, and the addition of JNK inhibitor SP600125 could inhibit the cell migration induced by Rap2. Our results suggest that Rap2 regulates cell migration through regulation of JNK activity and cellular localization.
【學(xué)位授予單位】：哈爾濱工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R329

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本文編號(hào)：1583151