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转基因小鼠中金属硫蛋白-生长抑素融合基因编码的前-前生长抑素的组织特异性翻译后加工。

Tissue-specific posttranslational processing of pre-prosomatostatin encoded by a metallothionein-somatostatin fusion gene in transgenic mice.

作者信息

Low M J, Hammer R E, Goodman R H, Habener J F, Palmiter R D, Brinster R L

出版信息

Cell. 1985 May;41(1):211-9. doi: 10.1016/0092-8674(85)90075-3.

DOI:10.1016/0092-8674(85)90075-3
PMID:2859927
Abstract

The somatostatins are neuropeptides of 14 and 28 amino acids that inhibit the release of growth hormone and other hypophyseal and gastrointestinal peptides. These neuropeptides are cleaved posttranslationally from a common precursor, pre-prosomatostatin. We report here the production and processing of pre-prosomatostatin by transgenic mice carrying a metallothionein-somatostatin fusion gene. The most active site of somatostatin production, as determined by hormone concentrations in the tissues, is the anterior pituitary, a tissue that does not normally synthesize somatostatin-like peptides. Anterior pituitary processed pre-prosomatostatin almost exclusively to the two biologically active peptides, somatostatin-14 and somatostatin-28, whereas the liver and kidney synthesized much smaller quantities of predominantly a 6000 dalton somatostatin-like peptide. The growth of the transgenic mice was normal despite high plasma levels of the somatostatin-like peptides. These studies indicate that proteases which cleave prosomatostatin to somatostatin-28 and somatostatin-14 are not specific to tissues that normally express somatostatin.

摘要

生长抑素是由14个和28个氨基酸组成的神经肽,可抑制生长激素以及其他垂体和胃肠肽的释放。这些神经肽是从共同的前体——前生长抑素原经翻译后加工产生的。我们在此报告携带金属硫蛋白-生长抑素融合基因的转基因小鼠对前生长抑素原的产生和加工情况。根据组织中的激素浓度确定,生长抑素产生的最活跃部位是垂体前叶,该组织通常不合成生长抑素样肽。垂体前叶几乎将前生长抑素原全部加工成两种具有生物活性的肽,即生长抑素-14和生长抑素-28,而肝脏和肾脏合成的数量要少得多,主要是一种6000道尔顿的生长抑素样肽。尽管转基因小鼠血浆中生长抑素样肽水平很高,但其生长正常。这些研究表明,将前生长抑素切割成生长抑素-28和生长抑素-14的蛋白酶并非正常表达生长抑素的组织所特有。

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