Seidah N G, Chrétien M
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, QC, Canada.
Curr Opin Biotechnol. 1997 Oct;8(5):602-7. doi: 10.1016/s0958-1669(97)80036-5.
Limited endoproteolysis of biologically inactive polypeptide precursors is a general mechanism generating a diversity of biologically active peptides and proteins in all eukaryotic phyla. One of the major recognition motifs involves cleavage at either specific single or pairs of basic residues of the general formula (R/K) - Xn - (R/K) decreases, where n = 0, 2, 4 or 6. Such sites are found in a variety of protein precursors in all eukaryotes, including those of endocrine and neural polypeptide hormones, enzymes, growth factors, receptors, adhesion molecules, viral glycoproteins, coagulation factors and even cell signaling molecules. A family of seven mammalian proteinases responsible for the processing of these proproteins has been recently identified. It comprises the proprotein convertases PC1/PC3, PC2, furin/PACE, PC4, PACE4, PC5/PC6 and PC7/SPC7/LPC/PC8. In a combinatorial fashion, these enzymes determine the cell-type and time at which biologically active products are derived from a given inactive precursor protein, thereby profoundly affecting cellular communication, differentiation and metabolic activity.
对无生物活性的多肽前体进行有限的内切蛋白水解是在所有真核生物门类中产生多种生物活性肽和蛋白质的普遍机制。主要识别基序之一涉及在通式为（R/K）-Xn-（R/K）的特定单个或成对碱性残基处进行切割，其中n = 0、2、4或6。在所有真核生物的多种蛋白质前体中都发现了此类位点，包括内分泌和神经多肽激素、酶、生长因子、受体、黏附分子、病毒糖蛋白、凝血因子甚至细胞信号分子的前体。最近已鉴定出一个由七种哺乳动物蛋白酶组成的家族，它们负责这些前体蛋白的加工。它包括前体蛋白转化酶PC1/PC3、PC2、弗林蛋白酶/PACE、PC4、PACE4、PC5/PC6和PC7/SPC7/LPC/PC8。这些酶以组合方式决定了从给定的无活性前体蛋白产生生物活性产物的细胞类型和时间，从而深刻影响细胞通讯、分化和代谢活性。
