Glucocorticoid Receptor: Structure, Expression, and Signal Transduction

糖皮质激素受体将荷尔蒙信号信息转化为基因转录的特定变化。我们克隆了大鼠糖皮质激素受体的编码序列，并对其功能结构域进行了鉴定。我们建议：(1)克隆野生型和突变型受体基因的基因组受体序列，鉴定受体启动子及其表达和调控，并试图将受体基因组织与其进化和功能联系起来；(2)探索信号转导的机制，特别是研究受体的DNA结合和核定位活性，并在整个转导过程中筛选突变体；(3)制备和纯化完整的受体和受体片段，用于受体、受体-激素和受体-DNA复合体的生化和大分子结构分析。这些研究将拓宽我们对信号转导和转录调控机制的理解。

Glucocorticoid receptors transduce hormonal signalling information into specific alterations in gene transcription. We have cloned the rat glucocorticoid receptor coding sequences and characterized its functional domains. Here we propose: (1) to clone genomic receptor sequences for wild type and mutant receptor genes, characterizing the receptor promoter and its expression and regulation, and attempting to relate receptor gene organization to its evolution and function; (2) to pursue the mechanism of signal transduction, characterizing in particular the DNA binding and nuclear localization activities of the receptor, and selecting mutants in the overall process of transduction; and (3) to produce and purify preparative amounts of intact receptor and receptor fragments for biochemical and macromolecular structural analyses of the receptor, receptor- hormone and receptor-DNA complexes. These studies will broaden our understanding of the mechanisms of signal transduction and transcriptional regulation.