Expression and processing of human preprogastrin in murine medullary thyroid carcinoma cells.
Expression and processing of human preprogastrin in murine medullary thyroid carcinoma cells.
复制标题
人前胃泌素前体在小鼠甲状腺髓样癌细胞中的表达和加工。
DOI：
10.1152/ajpgi.1991.260.5.g783
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Yamada,T
中科院分区：
文献类型：
--
作者：
Daugherty,DF;Dickinson,CJ;Takeuchi,T;Bachwich,D;Yamada,T
胃泌素是餐后胃酸分泌的主要激素介质，由其前体前胃泌素通过一系列翻译后加工反应（包括二元残基裂解和羧基末端 α-酰胺化）产生。前胃泌素包含三个二碱基裂解信号：Arg57Arg58、Lys74Lys75 和 Arg94Arg95，它们在不同组织中的裂解似乎不同。差异化加工是一种潜在的手段，通过它可以以组织特异性的方式调节生物活性肽的产生。为了进一步研究这些反应，我们使用 pZipNeo SV(X) 逆转录病毒载体在已知能够加工其他肽前体的异源细胞系 (MTC 6-23) 中表达人胃泌素 cDNA。用胃泌素 cDNA 逆转录病毒构建体 (pSVXgas) 转染的 psi 2 包装细胞系产生前胃泌素，但没有检测到大量加工过的酰胺化胃泌素。检测到加工过的酰胺化胃泌素的量。相比之下，用从 pSVXgas 转染的 psi 2 细胞上清液中获得的病毒原液感染的 MTC 6-23 细胞产生了所有标准分子形式的羧基末端酰胺化胃泌素，包括硫酸化和非硫酸化形式的三十三胃泌素 (G-34)、十七胃泌素 (G-17) 和十四胃泌素 (G-14)。这些研究表明，感染逆转录病毒肽 cDNA 构建体的异源内分泌细胞系可以作为肽激素翻译后加工的有用模型。
Gastrin, the primary hormonal mediator of postprandial gastric acid secretion, is produced from its precursor progastrin by a series of posttranslational processing reactions including dibasic residue cleavage and carboxyl-terminal alpha-amidation. Progastrin contains three dibasic cleavage signals, Arg57Arg58, Lys74Lys75, and Arg94Arg95, that appear to be cleaved differently in different tissues. Differential processing is a potential means by which the production of biologically active peptides may be regulated in a tissue-specific manner. To study these reactions further, we used the pZipNeo SV(X) retroviral vector to express human gastrin cDNA in a heterologous cell line (MTC 6-23) known to be capable of processing other peptide precursors. The psi 2 packaging cell line transfected with the gastrin cDNA-retroviral construct (pSVXgas) produced progastrin, but no substantial amounts of processed amidated gastrin were detected. amounts of processed amidated gastrin were detected. In contrast, MTC 6-23 cells infected with the viral stock obtained from the supernatant of pSVXgas-transfected psi 2 cells produced carboxyl-terminally amidated gastrin in all of its standard molecular forms, including sulfated and nonsulfated forms of tetratriacontagastrin (G-34), heptadecagastrin (G-17), and tetradecagastrin (G-14). These studies indicate that heterologous endocrine cell lines infected with a retroviral-peptide cDNA construct can serve as useful models for peptide hormone posttranslational processing.