Abstract

The fundamental objectives of the proposed program are to gain an understanding of the mechanisms by which cellular functions are regulated by protein phosphorylation and to elaborate on the role of protein phosphorylation as the mechanism of action of cAMP. In each area the control of glycogen metabolism will serve as a model system. We propose an investigation of the phosphorylation of phosphorylase kinase and glycogen synthase in the perfused rat heart so that we may identify and distinguish control processes mediated by cAMP and those otherwise regulated. That investigation is necessarily coordinated with the purification and physico-chemical characterization of cardiac phosphorylase kinase and glycogen synthase. These data will be correlated with studies of the isolated enzymes from the same tissues. In both the perfused heart system and the cultured muscle cells, we will probe key features of dibutyryl cAMP metabolism and mechanism of action and of cAMP-dependent protein kinase activation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK013613-18
Application #
3225087
Study Section
Biochemistry Study Section (BIO)
Project Start
1977-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
18
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618

  Publications

Zhao, J; Hoye, E; Boylan, S et al. (1998) Quaternary structures of a catalytic subunit-regulatory subunit dimeric complex and the holoenzyme of the cAMP-dependent protein kinase by neutron contrast variation. J Biol Chem 273:30448-59
Zhao, J; Trewhella, J; Corbin, J et al. (1997) Progressive cyclic nucleotide-induced conformational changes in the cGMP-dependent protein kinase studied by small angle X-ray scattering in solution. J Biol Chem 272:31929-36
Cawley, K C; Akita, C G; Angelos, K L et al. (1993) Characterization of the gene for rat phosphorylase kinase catalytic subunit. J Biol Chem 268:1194-200
Lee, J H; Maeda, S; Angelos, K L et al. (1992) Analysis by mutagenesis of the ATP binding site of the gamma subunit of skeletal muscle phosphorylase kinase expressed using a baculovirus system. Biochemistry 31:10616-25
Newsholme, P; Angelos, K L; Walsh, D A (1992) High and intermediate affinity calmodulin binding domains of the alpha and beta subunits of phosphorylase kinase and their potential role in phosphorylation-dependent activation of the holoenzyme. J Biol Chem 267:810-8
Henderson, S J; Newsholme, P; Heidorn, D B et al. (1992) Solution structure of phosphorylase kinase studied using small-angle X-ray and neutron scattering. Biochemistry 31:437-42
Cawley, K C; Akita, C G; Wineinger, M A et al. (1992) Coordinated expression of phosphorylase kinase subunits in regenerating skeletal muscle. J Biol Chem 267:17287-95
Newsholme, P; Walsh, D A (1992) A kinetic re-interpretation of the regulation of rabbit skeletal-muscle phosphorylase kinase activity by Ca2+ and phosphorylation. Biochem J 283 ( Pt 3):845-8
Walsh, D A; Newsholme, P; Cawley, K C et al. (1991) Motifs of protein phosphorylation and mechanisms of reversible covalent regulation. Physiol Rev 71:285-304
Cawley, K C; Akita, C G; Walsh, D A (1989) Expression of a cDNA for the catalytic subunit of skeletal-muscle phosphorylase kinase in transfected 3T3 cells. Biochem J 263:223-9

Showing the most recent 10 out of 11 publications