Abstract

The avian progesterone receptor is being used as a model for studying the role of phosphorylation in receptor structure and function. This receptor has been shown to be phosphorylated at multiple sites on serine residues and the extent of phosphorylation is rapidly increased following progesterone treatment. The present studies are designed to identify the actual sites of phosphorylation using biochemical techniques. In addition, studies will be initiated to reveal the structural or functional significance of phosphorylation through the analysis of mutant receptor forms. Intact receptor and a series of deletion mutants will be expressed in cultured cells. These will be compared with regard to hormone-dependent phosphorylation, physical properties, and biological activity. Eventually, the phosphorylation sites will be eliminated, individually or as a group, by use of serine replacement mutants. Such studies should provide a much more complete description of phosphorylation plus important clues on the biological significance of this event.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018287-09
Application #
3315330
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1983-09-01
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Smith, D F; Stensgard, B A; Welch, W J et al. (1992) Assembly of progesterone receptor with heat shock proteins and receptor activation are ATP mediated events. J Biol Chem 267:1350-6
Schowalter, D B; Sullivan, W P; Maihle, N J et al. (1991) Characterization of progesterone receptor binding to the 90- and 70-kDa heat shock proteins. J Biol Chem 266:21165-73
Kost, S L; Smith, D F; Sullivan, W P et al. (1989) Binding of heat shock proteins to the avian progesterone receptor. Mol Cell Biol 9:3829-38
Sullivan, W P; Madden, B J; McCormick, D J et al. (1988) Hormone-dependent phosphorylation of the avian progesterone receptor. J Biol Chem 263:14717-23
Dougherty, J J; Rabideau, D A; Iannotti, A M et al. (1987) Identification of the 90 kDa substrate of rat liver type II casein kinase with the heat shock protein which binds steroid receptors. Biochim Biophys Acta 927:74-80
Puri, R K; Toft, D O (1986) Peptide mapping analysis of the avian progesterone receptor. J Biol Chem 261:5651-7