The long-term objective of this research is to extend our understanding of the molecular mechanisms involved in the actions of glucocorticoids on their target tissues.
The aims of this proposal focus on characterizing the functional significance of glucocorticoid receptor phosphorylation with respect to ligand-binding activity and transformation to the DNA-binding state. Previous work has shown that the glucocorticoid receptor from murine L cells contains specific phosphoproteins, but very little is known about the role of receptor phosphate in hormone action. The glucocorticoids are widely used in the treatment of many diseases and characterizing the mechanisms by which their receptors are regulated constitutes a fundamental problem in molecular pharmacology. In the first series of experiments, the receptor will be isolated from 32P-labeled cells by a rapid immunoaffinity method using anti-receptor antibodies, and specific changes in receptor phosphorylation will be correlated with alterations in the binding capacity of the unoccupied receptor. The immuno-reactive, non-steroid-binding receptor from glucocorticoid-resistant variant cells will also be examined for changes in phosphorylation that render it unable to bind steroid. Additionally, these techniques will be used to examine particular changes in receptor phosphorylation during temperature-mediated transformation to the DNA-binding state. Another set of experiments will focus on characterizing the potential protein kinase activity of the receptor and determining if this activity is expressed by receptor covalently labeled with an irreversible glucocorticoid antagonist.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036905-03
Application #
3235499
Study Section
Endocrinology Study Section (END)
Project Start
1986-06-01
Project End
1990-05-31
Budget Start
1988-06-01
Budget End
1990-05-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Type
Schools of Medicine
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208