Posttranslational processing of gastrin.

Posttranslational processing of gastrin.
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胃泌素的翻译后加工。

DOI:
10.1152/physrev.1989.69.2.482
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发表时间:
1989
影响因子:
33.6
通讯作者:
Yamada,T
Yamada,T
中科院分区:
医学1区
文献类型:
--
作者:
Daugherty,D;Yamada,T

文献摘要

被引文献

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胃泌素在胃酸分泌的调节中起着核心作用。具有生物活性的胃泌素的主要分子形式是羧基末端酰胺化的十七肽 (G-17),由神经内分泌 G 细胞中较大的前体(前胃泌素)产生。这些细胞存在于胃窦粘膜、小肠粘膜和大肠粘膜以及中枢神经系统中。胃泌素产生细胞通过几种中间体处理前胃泌素,因为肽从内质网 (ER) 通过高尔基体堆栈分类到分泌囊泡。加工酶被划分为不同的细胞器并执行多种反应,包括信号肽裂解、酪氨酸-0-硫酸化、二碱基裂解和羧基末端铜酰胺化 (15, 16)。这些反应是许多神经内分泌肽激素加工过程中常见的反应。虽然肽激素的生物合成和释放可以在几个不同的水平上进行控制,但对含有 G 细胞的各种组织储存和释放不同分子形式的胃泌素的观察表明,翻译后加工机制在调节内分泌细胞中的重要性。肽加工的差异不仅在正常生理学中而且在病理条件下可能具有深远的重要性。
Gastrin plays a central role in the regulation of gastric acid secretion. The major molecular form of biologically active gastrin is a carboxyl-terminally amidated heptadecapeptide (G-17) produced from a larger precursor (progastrin) in neuroendocrine G-cells. These cells are found in the gastric antral mucosa, the small and large intestinal mucosa, and the central nervous system. Gastrin-producing cells process progastrin via several intermediates as the peptide is sorted from endoplasmic reticulum (ER) through the Golgi stack to secretory vesicles. Processing enzymes are compartmentalized to different organelles and perform numerous reactions, including signal peptide cleavage, tyrosine-0-sulfation, dibasic cleavage, and carboxyl-terminal cu-amidation (15, 16). These reactions are common to the processing of many neuroendocrine peptide hormones. Although peptide hormone biosynthesis and release can be controlled at several different levels, the observation that various tissues containing G-cells store and release different molecular forms of gastrin suggests the importance of posttranslational processing mechanisms in regulating endocrine cells. Differences in peptide processing may have profound importance not only in normal physiology but also in pathological conditions.