Jønson L, Johnsen A H
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Denmark.
Scand J Clin Lab Invest Suppl. 2001;234:87-92.
The vertebrate neuroendocrine peptide cholecystokinin (CCK) is subjected to numerous post-translational modifications upon maturation to bioactive CCK. However, the current knowledge of the proteolytic processing of proCCK, as reviewed here, is not complete. We have chosen Saccharomyces cerevisiae as a model to study these endoproteolytic processing events. Expression of proCCK as a fusion protein to the prepro leader peptide of alpha-mating factor directed the protein through the secretory pathway and resulted in nanomolar concentrations of secreted glycine-extended CCK. The CCK peptides showed many correlations to the known endoproteolytic processing products of proCCK in endocrine cells. Especially the processing to the abundant form, CCK-22, was investigated and it is suggested that a novel enzyme is responsible for its production. Thus, yeast may be used to study the proteolysis of proCCK with the aim to identify mammalian homologues involved in maturation of CCK.
脊椎动物神经内分泌肽胆囊收缩素（CCK）在成熟为生物活性CCK的过程中会经历多种翻译后修饰。然而，如本文所综述的，目前对前CCK蛋白水解加工的了解并不完整。我们选择酿酒酵母作为模型来研究这些内切蛋白水解加工事件。将前CCK作为融合蛋白与α-交配因子的前导肽表达，可引导该蛋白通过分泌途径，并产生纳摩尔浓度的分泌型甘氨酸延伸CCK。CCK肽与内分泌细胞中已知的前CCK蛋白水解加工产物有许多相关性。特别是对丰富形式的CCK-22的加工进行了研究，有人认为一种新的酶负责其产生。因此，酵母可用于研究前CCK的蛋白水解作用，以鉴定参与CCK成熟的哺乳动物同源物。
