新型分泌蛋白mLeg1与EGFR结合调控Akt信号

发布时间：2017-12-28 03:18

  本文关键词：新型分泌蛋白mLeg1与EGFR结合调控Akt信号　出处：《浙江大学》2016年博士论文　论文类型：学位论文

  更多相关文章： Leg1 唾液腺 肝脏 EGFR Akt 饥饿

【摘要】：Legl是所有脊椎动物中都保守存在的一个新型分泌蛋白,该蛋白靶向的组织器官不甚明了,同时整个蛋白序列只含功能未知的结构域DUF781,这对研究Legl的功能带来了极大的挑战。leg1在小鼠中同源基因mleg1的功能至今仍未被研究者们深入涉足研究。本课题通过Cre-LoxP系统获取mleg1的全身敲除小鼠(mleg1△/△),率先对mLeg1的功能进行深入的研究,希望对mLeg1以及Leg1蛋白家族的功能进行更深入和详细的研究。研究表明m Leg1在小鼠中主要在唾液腺表达,并分泌到唾液中,经过消化道进入血液循环,并最终对肝脏的功能进行调控。mLeg1可以直接与肝脏中的EGFR受体结合,激活EGFR/PI3K/Akt信号通路,从而对肝细胞的生理活动进行调节。本课题不仅对唾液腺如何对肝脏功能进行调控进行了详细的阐述,并且对全新的分泌蛋白mLeg1的功能进行了定义,确定一条以Le g1为起始,通过EGFR, PI3K激活Akt的一条全新的信号通路。此外,本研究发现小鼠中,饥饿可以诱导mleg1表达,并且该诱导表达通路在斑马鱼中同样保守存在。饥饿诱导表达的mLeg1可以将Akt的磷酸化水平维持在一定程度,从而对下游的包括p53降解在内的一系列细胞活动进行调控,在饥饿状态下对细胞发挥保护作用。综上所述,本课题对mleg1的功能进行了深度的拓展研究,确立了mLeg1/EGFR/PI3K/Akt的调控通路,该通路的意义之一在于饥饿状态下维持肝脏Akt的活性,对肝细胞进行保护。同时,本研究也为以后探究mLeg1在非饥饿状态下在生物体内的功能打下坚实的基础。
[Abstract]:Legl is a new secreted protein conserved in all vertebrates. The target protein is not clear. Meanwhile, the entire protein sequence contains only the unknown domain DUF781, which brings great challenges to the function of Legl. The function of leg1's homologous gene mleg1 in mice has not been studied in depth by the researchers. This paper gets the mleg1 system through the Cre-LoxP systemic knockout mice (mleg1 Delta / delta), first to conduct in-depth research on the function of mLeg1, hoping for more in-depth research and detailed functions of mLeg1 and Leg1 protein family. Studies have shown that m Leg1 is mainly expressed in salivary glands in mice, and secreted into saliva, through the digestive tract into the blood circulation, and ultimately regulate the function of the liver. MLeg1 can directly bind to the EGFR receptor in the liver and activate the EGFR/PI3K/Akt signaling pathway to regulate the physiological activities of the liver cells. This topic not only elaborates on how the salivary gland regulates liver function, but also defines the function of the new secretory protein mLeg1, and determines a new signal pathway starting with Le G1 and activating Akt through EGFR and PI3K. In addition, the study found that the expression of mleg1 was induced by starvation in mice, and the inducible expression pathway was also conserved in zebrafish. Starvation induced expression of mLeg1 can maintain the level of phosphorylation of Akt to a certain extent, thereby regulating downstream cell activities including p53 degradation, and protecting cells under starvation. To sum up, this topic has carried out a deep research on the function of mleg1, and established the regulatory pathway of mLeg1/EGFR/PI3K/Akt. One of the significances of this pathway is to maintain the activity of Akt in the liver under starvation condition and protect hepatocytes. At the same time, this study also lays a solid foundation for exploring the function of mLeg1 in the non starving state in the future.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q51

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1 胡敏杰;新型分泌蛋白mLeg1与EGFR结合调控Akt信号[D];浙江大学;2016年

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