The broad objective of this project is to understand the molecular basis for the control of intracellular events by extracellular signals. Glycogen metabolism in mammals has long provided an important model to study controls by hormones such as insulin, glucagon, and catecholamines. In this study, we propose to continue our research on the signaling pathways involved in controlling glycogen metabolism in the yeast Saccharomyces cerevisiae. Leading on from the progress of the last period, the specific aims are: (i) to study the yeast self-glucosylating proteins encoded by the GLG genes and their role in glycogen biosynthesis. We will focus on regulatory properties of these proteins; (ii) to identify novel glycogen synthase kinases and other regulatory proteins. To this end, we will use both classic biochemistry and yeast genetic screens; (iii) to investigate whether the cyclin dependent protein kinase Pho85p links nutrient sensing, glycogen accumulation and cell cycle control. We will seek to understand how Pho85p fits mechanistically with cAMP and Snf1p protein kinase controls of glycogen deposition; (iv) to investigate protein phosphatase involvement in the control of glycogen synthase and the role of the newly identified PIG1 gene. Over the last few years, there have been interesting examples of signal transduction pathways whose essential regulatory strategy is conserved between yeast and mammals. In the control of glycogen metabolism, we see some differences but also several intriguing parallels. This study of yeast may help give a broader perspective on intracellular signaling that can be relevant to the control of cellular events such as growth, proliferation and metabolism, in mammalian systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042576-09
Application #
2905413
Study Section
Physiological Chemistry Study Section (PC)
Program Officer
Sato, Sheryl M
Project Start
1991-01-04
Project End
2000-12-14
Budget Start
1999-07-01
Budget End
2000-12-14
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Biochemistry
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Roach, Peter J (2011) AMPK -> ULK1 -> autophagy. Mol Cell Biol 31:3082-4
Wilson, Wayne A; Roach, Peter J; Montero, Manuel et al. (2010) Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiol Rev 34:952-85
de Paula, Renato M; Wilson, Wayne A; Roach, Peter J et al. (2005) Biochemical characterization of Neurospora crassa glycogenin (GNN), the self-glucosylating initiator of glycogen synthesis. FEBS Lett 579:2208-14
de Paula, Renato Magalhaes; Wilson, Wayne A; Terenzi, Hector Francisco et al. (2005) GNN is a self-glucosylating protein involved in the initiation step of glycogen biosynthesis in Neurospora crassa. Arch Biochem Biophys 435:112-24
Torija, Maria-Jesus; Novo, Maite; Lemassu, Anne et al. (2005) Glycogen synthesis in the absence of glycogenin in the yeast Saccharomyces cerevisiae. FEBS Lett 579:3999-4004
Pederson, Bartholomew A; Wilson, Wayne A; Roach, Peter J (2004) Glycogen synthase sensitivity to glucose-6-P is important for controlling glycogen accumulation in Saccharomyces cerevisiae. J Biol Chem 279:13764-8
Wilson, Wayne A; Roach, Peter J (2003) Saccharomyces gene deletion project: applications and use in the study of protein kinases and phosphatases. Methods Enzymol 366:403-18
Wilson, Wayne A; Wang, Zhong; Roach, Peter J (2002) Analysis of respiratory mutants reveals new aspects of the control of glycogen accumulation by the cyclin-dependent protein kinase Pho85p. FEBS Lett 515:104-8
Roach, Peter J (2002) Glycogen and its metabolism. Curr Mol Med 2:101-20
Wilson, Wayne A; Wang, Zhong; Roach, Peter J (2002) Systematic identification of the genes affecting glycogen storage in the yeast Saccharomyces cerevisiae: implication of the vacuole as a determinant of glycogen level. Mol Cell Proteomics 1:232-42

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