ISOLATION AND CHARACTERIZATION OF PROGESTERONE RECEPTOR

当在胞浆提取物中处于非活性状态时，禽孕酮 受体，像大多数类固醇受体一样，与热休克复杂。 蛋白质HSP90。这种复合体不是通过简单的联想形成的， 但通过一个需要ATP水解和几个额外的 蛋白质。受体复合体中的其他蛋白质是HSP70和3 肽基丙酰异构酶或免疫亲和素。其中两个，FKBP52和 FKBP54结合免疫抑制药物FK506，第三个结合CYP-40 环孢素A受体复合体中的最后一种蛋白是p23，它是一种 独一无二的磷蛋白。我们在描述……方面取得了很大进展 受体复合体及其无细胞系统的开发 学习。拟议研究的目的是进一步加强我们的 对受体复合体组装、解离的认识 激素结合，以及受体的功能意义- 相关蛋白质。这将通过发展和 用于受体复合体形成的化学定义系统的操纵 使用纯化的蛋白质和特异的抗体探针。子复合体将 也被分析以描述络合物形成中的中间体和 各种蛋白质：发生的蛋白质相互作用。最后，酵母系统 与黄体酮受体的同源物将用于鉴定 酵母中的受体相关蛋白及其生物学特性的检测 该复合体中特定蛋白的诱变意义。这些 研究应该提供关于最早事件的新的和有价值的信息 在黄体酮的作用和腋下蛋白质中 事件。

When in its inactive form in cytosol extracts, the avian progesterone receptor, like most steroid receptors, is complexed with the heat shock protein hsp90. This complex does not form through a simple association, but through a process that requires ATP hydrolysis and several additional proteins. other proteins in the receptor complex are hsp70 and three peptidylprolyl isomerases or immunophilins. Two of these, FKBP52 and FKBP54, bind the immunosuppressant drug FK506 and the third, CyP-40, binds cyclosporin A. A final protein in the receptor complex is p23 which is a unique phosphoprotein. We have made much progress in the description of receptor complexes and in the development of cell-free systems for their study. The objective of the proposed studies is to further our understanding on the assembly of receptor complexes, their dissociation upon hormone binding, and the functional significance of the receptor- associated proteins. This will be accomplished through the development and manipulation of chemically defined systems for receptor complex formation using purified proteins and specific antibody probes. Sub-complexes will also be analyzed to describe intermediates in complex formation and the various protein:protein interactions that occur. Finally, a yeast system with progesterone receptor will be used to identify the homologs of receptor-associated proteins in yeast and to test the biological significance of specific proteins of the complex by mutagenesis. These studies should provide new and valuable information on the earliest events in progesterone action and the axillary proteins that are needed for these events.