The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors

The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors
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DOI:
10.1073/pnas.93.16.8374
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发表时间:
1996-08-06
影响因子:
11.1
通讯作者:
Tartaglia, LA
Tartaglia, LA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Baumann, H;Morella, KK;Tartaglia, LA

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瘦素受体(OB-R)是一种跨膜蛋白,介导瘦素(OB蛋白)的体重调节作用。OB-R基因的突变等位基因(Db)编码一种蛋白质,其胞质结构域被预测为功能不活跃。在不同的组织中已经检测到编码不同长度胞浆结构域的OB-Rs的几种mRNA剪接变异体。在这里,我们证明了全长OB-R(主要在下丘脑表达),但不是主要的自然发生的截断形式或在db/db小鼠中发现的突变形式,可以介导信号转导和转录激活(STAT)蛋白的激活,并通过白细胞介素6反应基因元件刺激转录。重建实验表明,尽管OB-R介导细胞内信号的特异性类似于白介素6型细胞因子受体,但信号传递似乎不依赖于白介素6型细胞因子受体的gp130信号转导成分。
The leptin receptor (OB-R) is a single membrane-spanning protein that mediates the weight regulatory effects of leptin (OB protein). The mutant allele (db) of the OB-R gene encodes a protein with a truncated cytoplasmic domain that is predicted to be functionally inactive. Several mRNA splice variants encoding OB-Rs with different length cytoplasmic domains have been detected in various tissues. Here we demonstrate that the full-length OB-R (predominantly expressed in the hypothalamus), but not a major naturally occurring truncated form or a mutant form found in db/db mice, can mediate activation of signal transducer and activator of transcription (STAT) proteins and stimulate transcription through interleukin 6 responsive gene elements. Reconstitution experiments suggest that, although OB-R mediates intracellular signals with a specificity similar to interleukin 6-type cytokine receptors, signaling appears to be independent of the gp130 signal transducing component of the interleukin 6-type cytokine receptors.