Baumann H, Morella K K, White D W, Dembski M, Bailon P S, Kim H, Lai C F, Tartaglia L A
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm, Buffalo, NY 14263, USA.
Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8374-8. doi: 10.1073/pnas.93.16.8374.
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 from 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.
瘦素受体（OB-R）是一种单次跨膜蛋白，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）编码一种细胞质结构域截短的蛋白质，预计该蛋白质功能失活。在各种组织中已检测到几种编码具有不同长度细胞质结构域的OB-R的mRNA剪接变体。在这里，我们证明全长OB-R（主要在下丘脑表达），而不是主要天然存在的截短形式或db/db小鼠中发现的突变体，能够介导信号转导和转录激活因子（STAT）蛋白的激活，并通过白细胞介素6反应性基因元件刺激转录。重组实验表明，虽然OB-R介导细胞内信号的特异性类似于白细胞介素6型细胞因子受体，但信号传导似乎独立于白细胞介素6型细胞因子受体的gp130信号转导成分。
