White D W, Kuropatwinski K K, Devos R, Baumann H, Tartaglia L A
Millennium Pharmaceuticals, Cambridge, Massachusetts 02215-2406, USA.
J Biol Chem. 1997 Feb 14;272(7):4065-71. doi: 10.1074/jbc.272.7.4065.
The leptin receptor (OB-R) mediates the weight regulatory effects of the adipocyte secreted hormone leptin (OB). Previously we have shown that the long form of OB-R, expressed predominantly in the hypothalamus, can mediate ligand-induced activation of signal transducer and activator of transcription factors 1, 3, and 5 and stimulate transcription via interleukin-6 and hematopoietin receptor responsive gene elements. Here we report that deletion and tyrosine substitution mutagenesis of OB-R identifies two distinct regions of the intracellular domain important for signaling. In addition, granulocyte-colony stimulatory factor receptor/OB-R and OB-R/granulocyte-colony stimulatory factor receptor chimeras are signaling competent and provide evidence that aggregation of two OB-R intracellular domains is sufficient for ligand-induced receptor activation. However, signaling by full-length OB-R appears to be relatively resistant to dominant negative repression by signaling-incompetent OB-R, suggesting that mechanisms exist to permit signaling by the long form of OB-R even in the presence [corrected] of excess naturally occurring short form of OB-R.
瘦素受体（OB-R）介导脂肪细胞分泌的激素瘦素（OB）的体重调节作用。此前我们已经表明，主要在下丘脑表达的长型OB-R能够介导配体诱导的信号转导和转录激活因子1、3和5的激活，并通过白细胞介素-6和造血因子受体反应性基因元件刺激转录。在此我们报告，OB-R的缺失和酪氨酸替代诱变确定了细胞内结构域中对信号传导重要的两个不同区域。此外，粒细胞集落刺激因子受体/OB-R和OB-R/粒细胞集落刺激因子受体嵌合体具有信号传导能力，并提供证据表明两个OB-R细胞内结构域的聚集足以实现配体诱导的受体激活。然而，全长OB-R的信号传导似乎相对抵抗无信号传导能力的OB-R的显性负抑制，这表明即使存在过量天然存在的短型OB-R，也存在允许长型OB-R进行信号传导的机制。
