Primary structure of rat HGF receptor and induced expression in glomerular mesangial cells
Primary structure of rat HGF receptor and induced expression in glomerular mesangial cells
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DOI：
10.1152/ajprenal.1996.271.3.f679
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发表时间：
1996-09-01
期刊：
影响因子：
--
通讯作者：
Dworkin, LD
中科院分区：
文献类型：
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作者：
Liu, YH;Tolbert, EM;Dworkin, LD
c-met 原癌基因编码肝细胞生长因子 (HGF) 的跨膜酪氨酸激酶受体。人们广泛认为，HGF 及其受体构成了旁分泌信号系统，其中间充质来源的细胞产生配体，该配体与主要在上皮来源的细胞上表达的受体结合。在这项研究中，我们从大鼠肾脏中分离出 c-met cDNA 的整个编码区并对其进行了完整测序。大鼠c-met cDNA的核苷酸序列显示，HGF受体在单一开放阅读框内编码为190kDa的跨膜糖蛋白，由1,382个氨基酸组成。各种组织中 c-met mRNA 水平的测定显示 c-met 广泛表达，在肾、肺和肝中水平最高。我们发现在原代培养的大鼠肾小球系膜细胞中白细胞介素-g (IL-6) 同时诱导 HGF 及其受体基因表达。将大鼠系膜细胞与IL-6一起孵育后，HGF和c-met的表达以时间和剂量依赖性方式显着刺激。我们的数据表明，HGF 的自分泌作用可能是通过在肾间充质细胞中同时诱导 HGF 及其受体表达来实现的。
The c-met protooncogene encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF). It has been widely suggested that HGF and its receptor constitute a paracrine signaling system, in which mesenchymally derived cells produce ligand that binds to the receptor predominantly expressed on cells of epithelial origin. In this study, we have isolated and completely sequenced the entire coding region of c-met cDNA from the rat kidney. The nucleotide sequence of the rat c-met cDNA revealed that the HGF receptor is encoded within single open-reading frame as 190 kDa of a transmembrane glycoprotein consisting of 1,382 amino acids. Determination of c-met mRNA levels in various tissues revealed a widespread expression of c-met with the highest levels in kidney, lung, and liver. We found simultaneous induction of both HGF and its receptor gene expression by interleukin-g (IL-6) in primary cultured rat glomerular mesangial cells. The expression of HGF and c-met was remarkably stimulated following incubation of rat mesangial cells with IL-6, in a time- and dose-dependent manner. Our data suggest that autocrine action of HGF may be achieved in vivo through simultaneous induction of both HGF and its receptor expression in renal mesenchymal cells.