Rouillé Y, Westermark G, Martin S K, Steiner D F
Howard Hughes Medical Institute, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3242-6. doi: 10.1073/pnas.91.8.3242.
Proglucagon is processed differentially in the pancreatic alpha cells and the intestinal L cells to yield either glucagon or glucagon-like peptide 1, respectively, structurally related hormones with opposing metabolic actions. Here, we have studied the processing of proglucagon in alpha TC1-6 cells, an islet-cell line transformed by simian virus 40 large tumor (T) antigen, a model of the pancreatic alpha cell. We found that these cells process proglucagon at certain dibasic cleavage sites to release glucagon and only small amounts of glucagon-like peptide 1, as demonstrated by both continuous and pulse-chase labeling experiments. Both normal islet alpha cells and alpha TC1-6 cells were shown to express the prohormone convertase PC2 at high levels, but not the related protease PC3. Expression of PC2 antisense RNA in alpha TC1-6 cells inhibited both PC2 production and proglucagon processing concomitantly. We conclude that PC2 is the key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype.
胰高血糖素原在胰腺α细胞和肠道L细胞中进行不同的加工处理，分别产生胰高血糖素或胰高血糖素样肽1，这两种结构相关的激素具有相反的代谢作用。在此，我们研究了胰高血糖素原在αTC1-6细胞中的加工处理情况，αTC1-6细胞是一种由猿猴病毒40大T抗原转化的胰岛细胞系，是胰腺α细胞的模型。我们发现，这些细胞在某些双碱性切割位点加工处理胰高血糖素原，以释放胰高血糖素，并且仅释放少量的胰高血糖素样肽1，连续标记实验和脉冲追踪标记实验均证明了这一点。正常胰岛α细胞和αTC1-6细胞均显示高水平表达激素原转化酶PC2，但不表达相关蛋白酶PC3。在αTC1-6细胞中表达PC2反义RNA可同时抑制PC2的产生和胰高血糖素原的加工处理。我们得出结论，PC2是负责具有α细胞表型的细胞中胰高血糖素原加工处理的关键内切蛋白酶。
