本文選題：RET　切入點(diǎn)：載體　出處：《鄭州大學(xué)》2005年碩士論文

【摘要】：RET(Rearranged during transfection)基因是1985年發(fā)現(xiàn)的在基因轉(zhuǎn)染過(guò)程中可以重排的基因。它具有20個(gè)外顯子。其中1號(hào)外顯子約為24kb,2-20號(hào)外顯子總計(jì)31kb。 RET轉(zhuǎn)錄產(chǎn)物經(jīng)過(guò)可變剪切后,形成5種RNA分子,經(jīng)過(guò)翻譯及翻譯后加工,可形成3種同型Ret蛋白。研究表明,大鼠胚胎早期,Ret高度表達(dá)于周?chē)�、中樞神�?jīng)系統(tǒng)、排泄系統(tǒng)等。胚胎中期,第四菱腦結(jié)節(jié)神經(jīng)嵴細(xì)胞、胚腎管細(xì)胞、腎上腺嗜鉻祖細(xì)胞、甲狀旁腺祖細(xì)胞均可發(fā)現(xiàn)RETmRNA高轉(zhuǎn)錄活性。 Ret蛋白是受體酪氨酸激酶(receptor turosine kinase,RTK)家族的一個(gè)新成員,為典型的TK結(jié)構(gòu)。Ret蛋白是膠質(zhì)細(xì)胞源性神經(jīng)生長(zhǎng)因子(GDNF)的受體,其主要的功能是將GDNF的信息向細(xì)胞內(nèi)傳遞。當(dāng)GDNF-GFRas-Ret復(fù)合物形成之后,Ret發(fā)生磷酸化激活,然后啟動(dòng)多種途徑,向細(xì)胞內(nèi)傳遞信息,從而調(diào)節(jié)神經(jīng)嵴細(xì)胞的增殖、分化、以及遷移到腸壁。RET的保守性及表達(dá)狀況是腸神經(jīng)系統(tǒng)、腎臟輸尿管芽形成及腎組織器官發(fā)育的早期遺傳學(xué)事件。研究表明,RET基因的突變、重排及缺失,與多發(fā)性?xún)?nèi)分泌腺瘤、乳突狀甲狀腺癌及先天性巨結(jié)腸密切相關(guān)。 在RET相關(guān)疾病中,多發(fā)性?xún)?nèi)分泌瘤2B(MEN2B)型病情最為嚴(yán)重。RET基因點(diǎn)突變是該病發(fā)生的分子事件。95%的患者的突變位點(diǎn)位于第16號(hào)外顯子上的918位密碼子處(cDNA第2753個(gè)堿基,由T變?yōu)镃),即Met(ATG)變?yōu)門(mén)hr(ACG)。由于該處是酶的催化中心,突變直接導(dǎo)致Ret蛋白胞內(nèi)部分構(gòu)象發(fā)生變化。在與沒(méi)有與相應(yīng)配體結(jié)合時(shí),自發(fā)激活,形成二聚體,產(chǎn)生磷酸化。最終激活下游信號(hào)分子,向胞內(nèi)傳遞信息,誘導(dǎo)細(xì)胞增生過(guò)度以至癌變。 關(guān)于MEN2B的研究,國(guó)內(nèi)外基本上局限于通過(guò)RT-PCR的方法獲得cDNA
[Abstract]:RET(Rearranged during transfectiongene was discovered in 1985 and can be rearranged during gene transfection.It has 20 exons.Exon 1 is about 24 kb / 2-20 exon in total 31 kb.Five RNA molecules were formed from RET transcripts after variable splicing. After translation and post-translational processing, three homotypic Ret proteins were formed.It has been shown that Ret is highly expressed in the peripheral central nervous system and excretory system in early embryonic rat.The high transcriptional activity of RETmRNA was found in midembryonic, fourth rhombohedral nodule neural crest cells, embryonic renal duct cells, adrenal chromaffin progenitor cells and parathyroid progenitor cells.Ret protein is a new member of the receptor tyrosine kinase receptor turosine kinase- rk family. It is a typical TK structure. Ret protein is the receptor of glial cell-derived nerve growth factor (GDNF). Its main function is to transfer the information of GDNF to the cells.After the formation of GDNF-GFRas-Ret complex, the activation of phosphorylation of ret and the initiation of multiple pathways to transmit information to the cells, thereby regulating the proliferation, differentiation, migration to the intestinal wall of the neural crest cells, and the conserved and expressed state of the intestinal nervous system.Early genetic events of renal ureteral bud formation and renal tissue and organ development.Studies have shown that mutations, rearrangements and deletions of the RET gene are closely associated with multiple endocrine adenomas, mastoid thyroid carcinoma and congenital megacolon.Among the RET related diseases, the most serious type of multiple endocrine tumor, 2Bmne2B). RET gene point mutation is the molecular event of the disease. 95% of the patients have mutation locus at the 918 codon on exon 16, which is located at the 2753 base of the codon.From T to C, I. e., Meta ATG, to THR ACGN.Because this site is the catalytic center of the enzyme, mutation directly leads to some conformation changes of Ret protein.When the ligand is not bound to the corresponding ligand, it spontaneously activates, forms dimer and produces phosphorylation.Finally, the downstream signaling molecules are activated to transmit information to the cell and induce hyperproliferation and carcinogenesis.The research on MEN2B is basically limited to obtaining cDNA by means of RT-PCR at home and abroad.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類(lèi)號(hào)】：R346

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