Davis S, Aldrich T H, Valenzuela D M, Wong V V, Furth M E, Squinto S P, Yancopoulos G D
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Science. 1991 Jul 5;253(5015):59-63. doi: 10.1126/science.1648265.
Although neurotrophic factors were originally isolated on the basis of their ability to support the survival of neurons, these molecules are now thought to influence many aspects of the development and maintenance of the nervous system. Identifying the receptors for these neurotrophic factors should aid in identifying the cells on which these factors act and in understanding their precise mechanisms of action. A "tagged-ligand panning" procedure was used to clone a receptor for ciliary neurotrophic factor (CNTF). This receptor is expressed exclusively within the nervous system and skeletal muscle. The CNTF receptor has a structure unrelated to the receptors utilized by the nerve growth factor family of neurotrophic molecules, but instead is most homologous to the receptor for a cytokine, interleukin-6. This similarity suggestes that the CNTF receptor, like the interleukin-6 receptor, requires a second, signal-transducing component. In contrast to all known receptors, the CNTF receptor is anchored to cell membranes by a glycosyl-phosphatidylinositol linkage.
尽管神经营养因子最初是根据其支持神经元存活的能力而分离出来的,但现在认为这些分子会影响神经系统发育和维持的许多方面。鉴定这些神经营养因子的受体应该有助于确定这些因子作用的细胞,并有助于理解它们精确的作用机制。一种“标记配体淘选”程序被用于克隆睫状神经营养因子(CNTF)的受体。这种受体仅在神经系统和骨骼肌中表达。CNTF受体的结构与神经营养分子神经生长因子家族所利用的受体无关,而是与一种细胞因子白细胞介素-6的受体最为同源。这种相似性表明,CNTF受体与白细胞介素-6受体一样,需要第二个信号转导成分。与所有已知受体不同,CNTF受体通过糖基磷脂酰肌醇连接锚定在细胞膜上。