本文關(guān)鍵詞：新型分泌蛋白mLeg1與EGFR結(jié)合調(diào)控Akt信號(hào)　出處：《浙江大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： Leg1 唾液腺 肝臟 EGFR Akt 饑餓

【摘要】：Legl是所有脊椎動(dòng)物中都保守存在的一個(gè)新型分泌蛋白,該蛋白靶向的組織器官不甚明了,同時(shí)整個(gè)蛋白序列只含功能未知的結(jié)構(gòu)域DUF781,這對(duì)研究Legl的功能帶來(lái)了極大的挑戰(zhàn)。leg1在小鼠中同源基因mleg1的功能至今仍未被研究者們深入涉足研究。本課題通過(guò)Cre-LoxP系統(tǒng)獲取mleg1的全身敲除小鼠(mleg1△/△),率先對(duì)mLeg1的功能進(jìn)行深入的研究,希望對(duì)mLeg1以及Leg1蛋白家族的功能進(jìn)行更深入和詳細(xì)的研究。研究表明m Leg1在小鼠中主要在唾液腺表達(dá),并分泌到唾液中,經(jīng)過(guò)消化道進(jìn)入血液循環(huán),并最終對(duì)肝臟的功能進(jìn)行調(diào)控。mLeg1可以直接與肝臟中的EGFR受體結(jié)合,激活EGFR/PI3K/Akt信號(hào)通路,從而對(duì)肝細(xì)胞的生理活動(dòng)進(jìn)行調(diào)節(jié)。本課題不僅對(duì)唾液腺如何對(duì)肝臟功能進(jìn)行調(diào)控進(jìn)行了詳細(xì)的闡述,并且對(duì)全新的分泌蛋白mLeg1的功能進(jìn)行了定義,確定一條以Le g1為起始,通過(guò)EGFR, PI3K激活A(yù)kt的一條全新的信號(hào)通路。此外,本研究發(fā)現(xiàn)小鼠中,饑餓可以誘導(dǎo)mleg1表達(dá),并且該誘導(dǎo)表達(dá)通路在斑馬魚中同樣保守存在。饑餓誘導(dǎo)表達(dá)的mLeg1可以將Akt的磷酸化水平維持在一定程度,從而對(duì)下游的包括p53降解在內(nèi)的一系列細(xì)胞活動(dòng)進(jìn)行調(diào)控,在饑餓狀態(tài)下對(duì)細(xì)胞發(fā)揮保護(hù)作用。綜上所述,本課題對(duì)mleg1的功能進(jìn)行了深度的拓展研究,確立了mLeg1/EGFR/PI3K/Akt的調(diào)控通路,該通路的意義之一在于饑餓狀態(tài)下維持肝臟Akt的活性,對(duì)肝細(xì)胞進(jìn)行保護(hù)。同時(shí),本研究也為以后探究mLeg1在非饑餓狀態(tài)下在生物體內(nèi)的功能打下堅(jiān)實(shí)的基礎(chǔ)。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：Q51

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1 胡敏杰;新型分泌蛋白mLeg1與EGFR結(jié)合調(diào)控Akt信號(hào)[D];浙江大學(xué);2016年

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本文編號(hào)：1344356