YEAST PEPTIDE PHEROMONES SYNTHESIS AND MODE OF ACTION

酵母菌的两种单倍体细胞类型(a和α) 每个酿酒酵母都会分泌特定的多肽激素样分子， 触发导致细胞融合(交配)的事件，相对 简单的发育顺序。因为敏锐的遗传和生化 研究可以在酵母细胞中进行，特别是那些利用 重组DNA，有可能了解到精确的分子细节 酵母菌对多肽激素生物合成和作用方式的影响 交配信息素(a因子和α因子)。应采取的方法 包括：(1)克隆的控制区的体外改变 α-因子和α-因子基因，以及新的指示基因融合 酶，以剖析细胞类型特异性的转录调控 这些基因；(2)特定的抗体、抑制物和突变，在 与克隆的基因结合，提供探针和底物 分析合成、膜转位、翻译后 信息素前体蛋白的加工和分泌运输 (前α因子和前α因子)；(3)[125I]-标记信息素， 反应性信息素衍生物的共价交联亲和力 使用基质结合信息素的层析，推测的基因 α-因子受体(STE2)和腺苷环化酶(CDC35)，并克隆了 STE5基因，鉴定信息素受体并探讨其作用机制 信息素对环状AMP合成的调节；以及，(4)转录映射， 基因破坏和DNA测序，以表征结构和 表达受信息素控制的克隆基因的功能。 在多细胞生物体中，多肽荷尔蒙负责细胞-细胞 在胚胎发育过程中和在 成人生活功能的协调性。生产不足或生产过剩 特定的多肽荷尔蒙，或无法感觉到它们的存在， 与许多人类疾病(如侏儒症、库兴氏病)有关 疾病和糖尿病)。理解基本方面的 多肽激素的合成和释放及其调节 过程，以及其作用机制的生化基础， 对于此类疾病的有效诊断和治疗是必要的。在……里面 此外，酵母信息素的生物合成知识可能会使 酵母菌发酵生产具有药用价值的人体激素 商业规模。

The two haploid cell types (a and Alpha) of the yeast Saccharomyces cerevisiae each secrete specific peptide hormone-like molecules which trigger events leading to fusion ("mating") of the cells, a relatively simple developmental sequence. Because incisive genetic and biochemical studies can be performed in yeast cells, particular those utilizing recombinant DNA, it may be possible to learn the precise molecular details of peptide hormone biosynthesis and mode of action by examining the yeast mating pheromones (a-factor and Alpha-factor). The approaches to be taken include: (1) in vitro alterations of the control regions of the cloned Alpha-factor and a-factor genes, and novel gene fusions to indicator enzymes, to dissect the cell type-specific regulation of transcription of these genes; (2) specific antibodies, inhibitors, and mutations, in conjunction with the cloned genes, to provide probes and substrates for analyzing the synthesis, membrane translocation, post-translational processing, and secretory transport of the pheromone precursor proteins (prepro-Alpha-factor and prepro-a-factor); (3) [125I]-labelled pheromones, covalent cross-linking of reactive pheromone derivatives, affinity chromatography using matrix-bound pheromones, putative genes for Alpha-factor receptor (STE2) and adenylate cyclase (CDC35), and the cloned STE5 gene, to identify pheromone receptors and to examine the mechanism of pheromonal modulation of cyclic AMP synthesis; and, (4) transcript mapping, gene disruption, and DNA sequencing, to characterize the structure and function of cloned genes whose expression is under pheromonal control. In multicellular organisms, peptide hormones are responsible for cell-cell communications that are required during embryonic development and in the coordination of life functions in adults. The under- or over-production of particular peptide hormones, or the inability to sense their presence, have been correlated with numerous human diseases (e.g. dwarfism, Cushing's disease, and diabetes). Understanding of the fundamental aspects of the synthesis and release of peptide hormones, and the regulation of these processes, as well as the biochemical bases of their mechanisms of action, is necessary for effective diagnosis and therapy of such diseases. In addition, knowledge of the biosynthesis of yeast pheromones may allow the production of medically-valuable human hormones by yeast cells on a commercial scale.