HORMONAL REGULATION OF ENZYME LEVELS IN MAMMALIAN TISSUE

这项研究的主要目的是确定 激素调节细胞溶质β-烯醇丙酮酸的基因表达 大鼠的羧基激酶 这将涉及进一步的表征 含有响应于以下的调节区的5 '-侧翼序列 cAMP和其他激素以及基因区域的鉴定 参与其组织特异性表达。 我们还计划隔离和 确定可能作为调节中间体参与的因素 β-烯醇式丙酮酸羧激酶基因的表达。 我们计划的具体主要目标是： 1.鉴定负责调节β-烯醇丙酮酸的序列 通过cAMP、胰岛素和糖皮质激素的羧激酶基因表达。 2.确定转录的激素调节中间体 β-烯醇式丙酮酸羧激酶基因的体外转录试验。 3.研究β-烯醇式丙酮酸羧激酶mRNA的成熟和周转。 4.确定负责组织特异性调节的序列， β-烯醇式丙酮酸羧激酶基因。 我们的长期目标是扩大我们对激素的了解， β-烯醇式丙酮酸羧激酶基因表达的调节，特别是在 糖尿病等疾病。 我们还计划制定新的程序， 在哺乳动物细胞中引入该基因的功能性拷贝， 研究其对特定组织中代谢途径的影响。

The broad aim of this research is to determine the mechanism by which hormones regulate the expression of the gene for cytosolic P-enolpyruvate carboxykinase from the rat. This will involve the further characterization of the 5'-flanking sequences which contain regulatory regions responsive to cAMP and other hormones and the identification of areas of the gene involved in its tissue specific expression. We also plan to isolate and identify factors which may be involved as intermediates in the regulation of P-enolpyruvate carboxykinase gene expression. Specific major goals of our program will be to: 1. Identify sequences responsible for regulation of P-enolpyruvate carboxykinase gene expression by cAMP, insulin and glucocorticoids. 2. Determine intermediates in the hormonal regulation of transcription of the P-enolpyruvate carboxykinase gene using in vitro transcription assays. 3. Study the maturation and turnover of P-enolpyruvate carboxykinase mRNA. 4. Identify sequences responsible for the tissue specific regulation of the P-enolpyruvate carboxykinase gene. Our long term objective is to extend our knowledge of the hormonal regulation of P-enolpyruvate carboxykinase gene expression especially in diseases such as diabetes. We also plan to develop new procedures for introducing functional copies of this gene in mammalian cells in order to study its effect on metabolic pathways in specific tissue.