HEMATOPOIETIC RECEPTORS AND HELICAL CYTOKINES
HEMATOPOIETIC RECEPTORS AND HELICAL CYTOKINES
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DOI：
10.1016/0167-5699(90)90139-z
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发表时间：
1990-10-01
期刊：
影响因子：
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通讯作者：
BAZAN, JF
中科院分区：
文献类型：
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作者：
BAZAN, JF
作为化学信使和细胞受体的各种蛋白质相互作用，控制血细胞1、2的生长速度和渐进分化过程，信使是淋巴因子、白介素类、集落刺激因子、生长激素和干扰素：一般而言，是细胞因子。调控对的第二个成分是跨膜受体pmteins：这些分子将同源细胞因子的特定结合转化为有丝分裂的细胞反应。在这篇文章中，费尔南多·巴赞讨论了细胞因子-受体相互作用的诱因结构模型，如果·正确的话，将改变人们对造血系统进化设计的看法。长期以来，人们的注意力集中在细胞因子-受体调节对2，3的细胞因子部分上，并得出结论，一系列不同的信号分子形成了一个功能破坏的基团，经常是冗余的，令人困惑的多效性活性4，5。因此，造血系统的调节电路类似于迷宫，而不是分层有序的金字塔2。3.细胞因子功能的明显复杂性掩盖了这样一个事实，即系统的生物活性物质是受体-细胞因子复合体；这种基本的相互作用是触发一系列细胞事件的触发器，最终导致细胞状态的可分析变化。限制对这一关键分子开关的研究可能是理解造血细胞调控的进化逻辑的关键。最近对一些细胞因子受体序列的表征揭示了调控基因的基本简单性的引人注目的图像6。这项工作认为，结合结构域的共同祖先是同源受体和结构相似的细胞因子之间在系统范围内、进化上保守的相互作用的有力线索。不同细胞因子之间特殊结构特征的保守意味着结合相互作用的结构密码的存在；然而，我认为这个密码的设计可能保证细胞因子和受体的基本水平的混杂。
Abewitching interplayofproteins, variously clothedas chemical messengers and cellular receptors, control the pace ofgrowth and the course of progressive differentiation in blood cell types1, 2, The messengers are, lymphokines, interleukins, colony" stimulating factors, growth hormones and interferons: generically, the cytokines. The second componentsofthe regulatory pairs are membrane-spanning receptor pmteins: these molecules transduce the specific binding ofcognate cytokines into a mitogenic cellular response. In this article, Fernando Bazan discusses aprovotative structural model for cytokine-receptor interactions which, if· correct, will alter perceptions of the evolutionary design ofthe haemopoietic system.For a long time attention has focused on the cytokine fraction of the cytokine-receptor regulatory pairs2, 3 and it has been concluded that an array of distinct signal molecules form a functionally corrupt group with often redundant, confusingly pleiotropic activities4, 5. Accordingly, the regulatory circuitry of the haemopoietic system resembles a maze rather than a hierarchically ordered pyramid2. 3. The apparent complexity of cytokine'functions' veils the fact that the bioactive agent of the system is the receptor-cytokine complex; this essential interaction is the trigger to a cascade of cellular events that culminate in assayable changes to the state of the cell. Restricting scrutiny to this pivotal molecular switch may be the key to understanding the evolutionary logic of haemopoietic cell regulation. The recent characterization of a number of the cytokine receptor sequences has revealed an arresting image of underlying simplicity to the regulatory maze6. This work argues that the common ancestry of binding domains is a strong clue to a systemwide, evolutionarily-conserved interaction between homologous receptors and structurally similar cytokines. The conservation of special structural features between disparate cytokines implies the existence of a structural code to the binding interaction; however, I suggest that the design of this code may guarantee a basal level of promiscuity to both cytokines and receptors.