Abstract

The aims of the proposd work are to investigate the roles of covalent enzyme phosphorylation of hepatic lipogenesis and the activity of the key rate-limiting enzyme of fatty acid synthesis, acetyl-CoA carboxylase. Particular emphasis is being placed on the characterization of site-specific phosphorylation changes in the enzyme indued by hormones in the intact cell and the characterization in vitro of the major site-specific protein kinases and phosphatases responsible for these alterations. In addition, the regulation of hepatic lipogenesis by insulin is being employed as a model system for the further elucidation of the molecular mechanism of insulin action..

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035712-04
Application #
3233965
Study Section
Metabolism Study Section (MET)
Project Start
1985-01-01
Project End
1988-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Dartmouth College
Department
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755

  Publications

Iseli, Tristan J; Oakhill, Jonathan S; Bailey, Michael F et al. (2008) AMP-activated protein kinase subunit interactions: beta1:gamma1 association requires beta1 Thr-263 and Tyr-267. J Biol Chem 283:4799-807
Anderson, Kristin A; Ribar, Thomas J; Lin, Fumin et al. (2008) Hypothalamic CaMKK2 contributes to the regulation of energy balance. Cell Metab 7:377-88
Barre, Laura; Richardson, Christine; Hirshman, Michael F et al. (2007) Genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation. Am J Physiol Endocrinol Metab 292:E802-11
Ho, Richard C; Fujii, Nobuharu; Witters, Lee A et al. (2007) Dissociation of AMP-activated protein kinase and p38 mitogen-activated protein kinase signaling in skeletal muscle. Biochem Biophys Res Commun 362:354-9
Rockl, Katja S C; Hirshman, Michael F; Brandauer, Josef et al. (2007) Skeletal muscle adaptation to exercise training: AMP-activated protein kinase mediates muscle fiber type shift. Diabetes 56:2062-9
Folmes, Karalyn D; Witters, Lee A; Allard, Michael F et al. (2007) The AMPK gamma1 R70Q mutant regulates multiple metabolic and growth pathways in neonatal cardiac myocytes. Am J Physiol Heart Circ Physiol 293:H3456-64
Hallows, Kenneth R; Fitch, Adam C; Richardson, Christine A et al. (2006) Up-regulation of AMP-activated kinase by dysfunctional cystic fibrosis transmembrane conductance regulator in cystic fibrosis airway epithelial cells mitigates excessive inflammation. J Biol Chem 281:4231-41
Hurley, Rebecca L; Barre, Laura K; Wood, Sumintra D et al. (2006) Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP. J Biol Chem 281:36662-72
Iseli, Tristan J; Walter, Mark; van Denderen, Bryce J W et al. (2005) AMP-activated protein kinase beta subunit tethers alpha and gamma subunits via its C-terminal sequence (186-270). J Biol Chem 280:13395-400
Konrad, D; Rudich, A; Bilan, P J et al. (2005) Troglitazone causes acute mitochondrial membrane depolarisation and an AMPK-mediated increase in glucose phosphorylation in muscle cells. Diabetologia 48:954-66

Showing the most recent 10 out of 77 publications