PHYSIOLOGY OF THYROID HORMONE DEPENDENT GENE EXPRESSION

描述(改编自申请人的摘要)：本报告的重点 建议是检查行动中的关键组件，这些组件可能 导致组织特异性。结构和生物化学解释 关于α1和β1受体之间的功能差异 单独使用嵌合的α1-β1和突变的受体 与其他配体依赖和组织特异性核的相互作用 蛋白质将被测定。关键的半碱基序列和基序 大鼠α-肌球蛋白重链和苹果酸的TRE排列 酶基因将与大鼠生长激素中定义的基因进行比较。 基因。两种受体的生化相互作用和功能 具有所有三个TRE的信息丰富的突变体将被分析。瞬变 将使用转染系统来改变数量、类型和比例 正常和突变的受体以及报告基因上游的tRes 基因。细胞将暴露在TH中以检查生物 组织特异性差异TH受体(Thr)的意义 甲状腺功能正常的大鼠体内存在饱和现象。

DESCRIPTION (adapted from applicant's abstract): The focus of this proposal is to examine the critical components in TH action which might result in tissue specificity. The structural and biochemical explanations for the functional differences between the alpha 1 and beta 1 receptors using chimeric alpha 1-beta 1 and mutated receptors both alone and during interactions with other ligand-dependent and tissue specific nuclear proteins will be determined. The critical half-site sequences and motif arrangements of TREs from the rat alpha myosin heavy chain and malic enzyme genes will be compared to those defined in the rat growth hormone gene.The biochemical interactions of the two receptors and functionally informative mutants with all three TREs will be analyzed. Transient transfection systems will be used to vary the quantity, type, and ratio of normal and mutant receptors as well as TREs upstream of the reporter genes. Cells will be exposed to THs to examine the biological significance of the tissue specific, differential TH receptor (THR) saturation present in euthyroid rats.