Yang S H, Dickson A J
Biochemistry Research Division, 2.205 School of Biological Sciences, University of Manchester, U.K.
Biochem J. 1995 Sep 1;310 ( Pt 2)(Pt 2):375-8. doi: 10.1042/bj3100375.
Gene 33 and phosphoenolpyruvate carboxykinase (PEPCK) present excellent model systems for the analysis of the differential control of hepatic gene expression by the insulin-regulated signal-transduction pathway(s). We have analysed the importance of specific components in the insulin-regulated transduction pathway(s) towards enhanced gene expression (gene 33) and inhibited gene expression (PEPCK) by examination of the influence of selective inhibitors. Rapamycin, which inhibits the 70 kDa S6 kinase (p70rsk) does not influence the actions of insulin on gene 33 or PEPCK; thus the kinase p70rsk appears to play no direct role in the regulation of expression of these two hepatic genes. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, differentiates between processes involved in insulin regulation of gene 33 and PEPCK mRNA expression. Although the actions of insulin on gene 33 expression are abolished by wortmannin, the actions of insulin on PEPCK expression are insensitive to wortmannin. The existence of wortmannin-sensitive and rapamycin/wortmannin-insensitive pathways for transducing insulin signals to factors controlling gene expression, and the differential actions on specific genes, presents an initial step towards deciphering the linkage between signalling components and selective control of gene expression.
基因33和磷酸烯醇式丙酮酸羧激酶（PEPCK）是用于分析胰岛素调节信号转导途径对肝脏基因表达的差异控制的优秀模型系统。我们通过研究选择性抑制剂的影响，分析了胰岛素调节信号转导途径中特定成分对增强基因表达（基因33）和抑制基因表达（PEPCK）的重要性。抑制70 kDa S6激酶（p70rsk）的雷帕霉素不影响胰岛素对基因33或PEPCK的作用；因此，激酶p70rsk似乎在这两个肝脏基因表达的调节中不发挥直接作用。渥曼青霉素是磷脂酰肌醇3激酶的抑制剂，它区分了胰岛素调节基因33和PEPCK mRNA表达所涉及的过程。虽然渥曼青霉素消除了胰岛素对基因33表达的作用，但胰岛素对PEPCK表达的作用对渥曼青霉素不敏感。存在将胰岛素信号转导至控制基因表达的因子的渥曼青霉素敏感和雷帕霉素/渥曼青霉素不敏感途径，以及对特定基因的差异作用，是解读信号成分与基因表达选择性控制之间联系的第一步。
