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斑马鱼信号转导与转录激活因子3(Stat3)在胚胎发育过程中于特定组织中表达,且信号转导与转录激活因子1(Stat1)可在STAT1缺陷的人类细胞系中挽救细胞因子信号传导。

Zebrafish stat3 is expressed in restricted tissues during embryogenesis and stat1 rescues cytokine signaling in a STAT1-deficient human cell line.

作者信息

Oates A C, Wollberg P, Pratt S J, Paw B H, Johnson S L, Ho R K, Postlethwait J H, Zon L I, Wilks A F

机构信息

Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia.

出版信息

Dev Dyn. 1999 Aug;215(4):352-70. doi: 10.1002/(SICI)1097-0177(199908)215:4<352::AID-AJA7>3.0.CO;2-J.

Abstract

Transcription factors of the STAT family are required for cellular responses to multiple signaling molecules. After ligand binding-induced activation of cognate receptors, STAT proteins are phosphorylated, hetero- or homodimerize, and translocate to the nucleus. Subsequent STAT binding to specific DNA elements in the promoters of signal-responsive genes alters the transcriptional activity of these loci. STAT function has been implicated in the transduction of signals for growth, reproduction, viral defense, and immune regulation. We have isolated and characterized two STAT homologs from the zebrafish Danio rerio. The stat3 gene is expressed in a tissue-restricted manner during embryogenesis, and larval development with highest levels of transcript are detected in the anterior hypoblast, eyes, cranial sensory ganglia, gut, pharyngeal arches, cranial motor nuclei, and lateral line system. In contrast, the stat1 gene is not expressed during early development. The stat3 gene maps to a chromosomal position syntenic with the mouse and human STAT3 homologs, whereas the stat1 gene does not. Despite a higher rate of evolutionary change in stat1 relative to stat3, the stat1 protein rescues interferon-signaling functions in a STAT1-deficient human cell line, indicating that cytokine-signaling mechanisms are likely to be conserved between fish and tetrapods. Dev Dyn 1999;215:352-370.

摘要

STAT家族的转录因子是细胞对多种信号分子作出反应所必需的。在配体结合诱导同源受体激活后,STAT蛋白被磷酸化,形成异源或同源二聚体,并转位至细胞核。随后,STAT与信号反应基因启动子中的特定DNA元件结合,改变这些基因座的转录活性。STAT功能涉及生长、繁殖、病毒防御和免疫调节等信号的转导。我们从斑马鱼(Danio rerio)中分离并鉴定了两个STAT同源物。stat3基因在胚胎发育和幼体发育过程中以组织限制性方式表达,在前原胚层、眼睛、颅感觉神经节、肠道、咽弓、颅运动核和侧线系统中检测到最高水平的转录本。相比之下,stat1基因在早期发育过程中不表达。stat3基因定位于与小鼠和人类STAT3同源物同线的染色体位置,而stat1基因则不然。尽管相对于stat3,stat1的进化变化率更高,但stat1蛋白可在STAT1缺陷的人类细胞系中拯救干扰素信号功能,这表明鱼类和四足动物之间细胞因子信号传导机制可能是保守的。《发育动力学》1999年;215:352 - 370。

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