Laporte S, Denault J B, D'Orléans-Juste P, Leduc R
Department of Pharmacology, Medical School, Université de Sherbrooke, Québec, Canada.
J Cardiovasc Pharmacol. 1993;22 Suppl 8:S7-10. doi: 10.1097/00005344-199322008-00004.
Recently it was documented that furin, a calcium-dependent serine endoprotease, cleaves many protein precursors at pairs of basic amino acids, thus liberating the biologically active peptides. The endothelin precursors follow a biosynthetic pathway similar to these proteins, where the precursor is initially processed to the intermediate, big endothelin (big ET) before its conversion to the endothelin (ET) peptide. Analysis of the amino acid sequence of the endothelin pro-proteins shows that they are susceptible to processing by endoproteases that cleave at pairs of basic amino acids. For example, human endothelin-1 (ET-1) precursor possesses a typical furin cleavage site motif (Arg-X-Lys/Arg-Arg) at the following residues: Arg32-Ser33-Lys34-Arg35 and Arg72-Ser73-Lys74-Arg75. We have isolated mRNA from cultured bovine endothelial cells and, using a human furin cRNA probe, shown that a furin mRNA of 4.5 kb is present in these cells. We propose that furin, a novel endoprotease belonging to the mammalian subtilisin family of serine proteases, may be implicated in the processing of pro-endothelin precursors, liberating big ET.
最近有文献记载，弗林蛋白酶（一种钙依赖性丝氨酸内切蛋白酶）可在碱性氨基酸对处切割许多蛋白质前体，从而释放出生物活性肽。内皮素前体遵循与这些蛋白质相似的生物合成途径，在此途径中，前体首先被加工成中间体大内皮素（big ET），然后再转化为内皮素（ET）肽。对内皮素原蛋白的氨基酸序列分析表明，它们易被在碱性氨基酸对处切割的内切蛋白酶加工。例如，人内皮素-1（ET-1）前体在以下残基处具有典型的弗林蛋白酶切割位点基序（Arg-X-Lys/Arg-Arg）：Arg32-Ser33-Lys34-Arg35和Arg72-Ser73-Lys74-Arg75。我们从培养的牛内皮细胞中分离出了mRNA，并使用人弗林蛋白酶cRNA探针表明这些细胞中存在4.5 kb的弗林蛋白酶mRNA。我们提出，弗林蛋白酶是一种属于哺乳动物枯草杆菌蛋白酶家族的新型丝氨酸蛋白酶，可能参与前内皮素前体的加工，释放出大内皮素。
