Studies involving small eukaryotes like baker's yeast, Saccharomyces cerevisiae have frequently provided great insights into the function of cellular components that are found in all eukaryotic organisms, including humans. Examples include mitotic cell cycle control by p34cdc2 protein kinase and function of the RAS oncogene. Glycogen accumulation in yeast cells is the last step in a pathway that is sensitive to a variety of inputs. We have studied components that participate in regulation of glycogen metabolism and found that it is regulated in part by cAMP-dependent protein kinase and by type 1 protein phosphatase (PP1). Further study of this protein phosphatase revealed that it apparently plays a greater role in the cell; it modulates some aspects of the cell division cycle and protein translation initiation. This proposal concentrates on defining roles of PP1 by a two-fold attack. PP1 is known to bind to proteins that regulate its activity and subcellular location. Mutations in the PP1 gene, GLC7, that exhibit specific traits will define functional parts of this highly conserved protein. These parts include binding sites for regulatory proteins as well as catalytically important residues. Temperature-sensitive glc7 mutations will also be used to clarify steps in the cell division cycle at which PP1 activity is critical. In the second prong of this attack, the PP1 regulatory and binding proteins will be identified biochemically and genetically. Consequences of mutations in these genes will reveal the roles that they play in PP1 function. Mutations in the GLC6 gene were found to either increase or decrease glycogen levels. These mutations also controlled which sugars (carbon sources) cells could grow on. The last part of this proposal focuses on elucidating the function of GLC6. The available evidence indicates that GLC6 participates in regulating cellular metabolism based on carbon source. Such regulation is defective in humans with noninsulin-dependent diabetes mellitus.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040326-07
Application #
2180261
Study Section
Biochemistry Study Section (BIO)
Project Start
1988-07-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211