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.
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