Bazan J F
Department of Biochemistry and Biophysics, School of Medicine, University of California, San Francisco 94143-0448.
Neuron. 1991 Aug;7(2):197-208. doi: 10.1016/0896-6273(91)90258-2.
Among the molecules that determine the developmental fate of sympathetic neurons from noradrenergic to cholinergic function are two apparently unrelated proteins, cholinergic differentiation factor and ciliary neurotrophic factor (CDF and CNTF, respectively). The present work suggests a structural basis for their functional overlap: sequence pattern-matching and predictive structure analysis contends that CDF and CNTF are homologous and share a common helical framework. An integrated CDF/CNTF profile also reveals similar sequence/structure motifs in a group of hematopoietic cytokines composed of granulocyte colony-stimulating factor, interleukin-6, and a novel factor called oncostatin M; a more distant relationship is indicated with interleukin-3 and interferons-alpha/beta. Evolutionary ties between neuropoietic and hematopoietic cytokines predict a distinctive tertiary architecture for the uncharacterized CDF and CNTF receptors. The intertwined cytokine/receptor networks signal a closer relationship between the molecular mechanisms underlying neuro- and hematopoiesis.
在决定交感神经元从去甲肾上腺素能功能向胆碱能功能发育命运的分子中，有两种明显不相关的蛋白质，即胆碱能分化因子和睫状神经营养因子（分别为CDF和CNTF）。目前的研究揭示了它们功能重叠的结构基础：序列模式匹配和预测结构分析表明，CDF和CNTF是同源的，并且共享一个共同的螺旋框架。综合的CDF/CNTF图谱还揭示了一组造血细胞因子中相似的序列/结构基序，这些造血细胞因子包括粒细胞集落刺激因子、白细胞介素-6以及一种名为制瘤素M的新因子；与白细胞介素-3和α/β干扰素的关系则更为疏远。神经生成性细胞因子和造血细胞因子之间的进化联系预示着未被表征的CDF和CNTF受体具有独特的三级结构。相互交织的细胞因子/受体网络表明神经生成和造血作用背后的分子机制之间存在更紧密的关系。
