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- W2215768275 abstract "1.1 STAT3分子的结构和功能 STAT3蛋白大约由770个氨 基酸组成,有三种异构体:STAT3α(即一般意义所指 的STAT3)、STAT3β和STAT3γ。STATs分子结构相似, 被分成与功能相关的几个结构域,从氨基端到羧基端 依次为:氨基末端结构域、coiled-coil结构域、DNA结 合结构域、linker结构域、SH2结构域(Src-homology-2 domain)、羧基末端转录活化结构域(transcriptional activation domain, TAD)。Caldenhoven等从嗜酸性粒细 胞cDNA文库中分离并克隆了STAT3异构体STAT3β,同 STAT3α相比,STAT3β在羧基端第2145位-第2195位少50个 碱基对,导致其蛋白末端55个氨基酸残基被7个独特的氨 基酸残基所替代。STAT3γ是STAT3α的限制性蛋白水解产 物,它不具有STAT3α末端的TAD,是STAT3α的一种显性 阴性异构体。 STAT3在早期胚胎发育和许多正常组织分化中发挥 着不可缺少的重要作用。它广泛存在于不同类型的细 胞和组织中,在大脑、心脏、肝脏、睾丸和胸腺等组织 中含量较高,在脾脏中也可检出。此外,STAT3还参与细 胞生长、分化、恶性转化及凋亡抑制等活动的调控。 1.2 JAK-STAT信号通路的概念及生理作用 JAK蛋白酪氨 酸激酶(Janus protein tyrosine kinase)是近些年来鉴定出 来的在细胞因子信号传递过程中起重要作用的蛋白酪氨 酸激酶。它可在细胞因子受体与相应配基结合后活化, 并进而激活另一种信号蛋白分子“信号转导子和转录激活 子”(signal transducer and activator of transcription, STATs), 从而起到诱导目的基因表达的作用。JAK蛋白酪氨酸激 酶家族共包括4个成员:JAK1、JAK2、JAK3和TYK2。而 STATs家族成员则有STAT1、STAT2、STAT3、STAT4、 STAT5a、STAT5b和STAT6,分别由不同的基因编码。 STATs被JAK磷酸化后发生二聚化,然后穿过核膜进入核 内调节相关基因的表达,这条信号通路称为JAK-STAT信 号通路。STATs蛋白广泛表达于机体不同类型的细胞和组 织中,参与细胞生长、分化、凋亡等多种生理功能的调 控,并与炎症、肿瘤和免疫反应关系密切。 1.3 JAK-STAT信号通路的激活及调节 1.3.1 JAK-STAT信号通路的激活 目前研究显示,多种细 胞外蛋白可与细胞膜表面的特异受体结合,通过酪氨 酸激酶(常为JAK家族成员,包括JAK1、JAK2、JAK3和 TYK2,有时是Src家族成员)使受体酪氨酸磷酸化而活 化,进而激活胞浆中的STAT3分子,这些STAT单体即形 成同源或异源二聚体而作为转录因子进入细胞核调控 作者单位:250021 济南,山东大学附属省立医院胸外科(通讯作者: 王洲,E-mail: wz620226@hotmail.com) ·综 述·" @default.
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- W2215768275 date "2010-02-01" @default.
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- W2215768275 title "[Advances of the correlation between JAK-STAT3 signaling pathway and the biological behavior of non-small cell lung cancer]." @default.
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- W2215768275 doi "https://doi.org/10.3779/j.issn.1009-3419.2010.02.16" @default.
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