The PI is currently studying the regulation of the cyclin- dependent the regulation of the cyclin-dependent kinase Pho85 in mediating a response to nutritional status and glycogen accumulation. The PI has been studying PHO85 for a number of years, cloning and sequencing genes involved in phosphate metabolism and isolating mutations in Pho85, the kinase, originally identified as a regulator of phosphate metabolism. Recent work from other laboratories defined Pho85 as a cyclin dependent kinase that interacts with different cyclin-like molecules to regulate phosphate metabolism and to perform as yet undefined functions in other aspects of metabolism. While the PIs early studies had not shed much light on the mechanism of Pho85 action, in the course of his more recent analysis of Pho85, the PI made the exciting and novel discovery that a pho85 deletion strain hyperaccumulates glycogen in nutrient rich media, conditions which normally repress glycogen synthesis. Little is known about the signaling pathway involving Pho85 and glycogen accumulation and the potential role of cAMP in regulating Pho activity. The PI has substantial preliminary evidence supporting a model in which Pho85 directly inhibits glycogen accumulation through inhibitory phosphorylation of defined sites in glycogen synthase. He proposes to try to identify the regulatory cyclin for Pho85 that is involved in this catalysis. In addition, he proposes to analyze the role of a cyclin-like molecule Cig1 which he identified through two hybrid analysis as interacting with Pho85 and has shown is required for glycogen accumulation . Finally, the PI proposes to analyze the mechanism by which Pho81, a putative inhibitor of Pho85 is regulated by phosphorylation by Pho85.
| Waters, Norman C; Knight, Janine P; Creasy, Caretha L et al. (2004) The yeast Pho80-Pho85 cyclin-CDK complex has multiple substrates. Curr Genet 46:1-9 |
| Knight, Janine P; Daly, Thomas M; Bergman, Lawrence W (2004) Regulation by phosphorylation of Pho81p, a cyclin-dependent kinase inhibitor in Saccharomyces cerevisiae. Curr Genet 46:10-9 |
