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小鼠白细胞介素-6受体相关信号转导子gp130的分子克隆及其在体内的表达调控

Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo.

作者信息

Saito M, Yoshida K, Hibi M, Taga T, Kishimoto T

机构信息

Division of Immunology, Institute for Molecular and Cellular Biology, Osaka University, Japan.

出版信息

J Immunol. 1992 Jun 15;148(12):4066-71.

PMID:1602143
Abstract

The IL-6R system comprises two functionally different chains: a ligand binding-chain (IL-6R) and a non-ligand-binding but signal-transducing chain (gp130). gp130 associates with the IL-6-IL-6R complex, resulting in the formation of high-affinity IL-6 binding sites, and transduces the signal. A cDNA for murine gp130 has been cloned from the cDNA library of murine macrophages by using a human gp130 cDNA as a probe. The overall homology with human gp130 was 76.8% at the protein level. The extracellular region of murine gp130, as observed in human gp130, comprises 6 U of a fibronectin type III module and part of this region of approximately 200 amino acids has typical features of a cytokine receptor family. Cloned murine gp130 could transduce the growth signal in a murine IL-3-dependent cell line in response to a complex of IL-6 and soluble IL-6R. Two species of murine gp130 mRNA (7 and 10 kb) were expressed in almost all the cell lines. These transcripts were also ubiquitously expressed in murine tissues, embryonic stem cells, and embryos as early as day 6 of gestation. Administration of IL-6 in mouse caused up-regulation of the gp130 mRNA levels in several tissues. Both gp130 and IL-6R mRNA in liver were up-regulated in vivo by IL-6.

摘要

白细胞介素-6受体(IL-6R)系统由两条功能不同的链组成:一条配体结合链(IL-6R)和一条非配体结合但能转导信号的链(gp130)。gp130与IL-6-IL-6R复合物结合,导致形成高亲和力的IL-6结合位点,并转导信号。通过使用人gp130 cDNA作为探针,从小鼠巨噬细胞的cDNA文库中克隆出了小鼠gp130的cDNA。在蛋白质水平上,与人类gp130的总体同源性为76.8%。正如在人类gp130中所观察到的那样,小鼠gp130的细胞外区域包含6个纤连蛋白III型模块单位,该区域中约200个氨基酸的部分具有细胞因子受体家族的典型特征。克隆的小鼠gp130能够在小鼠IL-3依赖的细胞系中响应IL-6和可溶性IL-6R的复合物转导生长信号。两种小鼠gp130 mRNA(7 kb和10 kb)在几乎所有细胞系中均有表达。这些转录本在小鼠组织、胚胎干细胞和胚胎中也广泛表达,早在妊娠第6天就已出现。在小鼠中给予IL-6会导致几种组织中gp130 mRNA水平上调。在体内,IL-6可使肝脏中的gp130和IL-6R mRNA上调。

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