In this proposal, the incorporation of molecular analysis and animal studies will be used to address the regulation of the nuclear orphan receptor Nur77. The primary goal of this proposal is to demonstrate how differential phosphorylation of Nur77 can serve as a central control point between extracellular signaling pathways and Nur77 action, which will be accomplished by the following specific aims: 1. To determine the functional consequences of Nur77 phosphorylation., and 2. To address the role of phosphorylation in the regulation of Nur77 by physiological responses in animals. Experiments will address how modifications of Nur77 by adrenocorticotropin hormone (ACTH) mediate Nur77 transcriptional activity and target gene specificity in addition to examining how modification of Nur77 is regulated by physiological stress responses in rodents.
