Abstract

The objective of these studies is to delineate the molecular mechanism by which the phosphorylation state of skeletal muscle glycogen synthase is altered in diabetes and by insulin treatment. Emphasis will be focused on those protein kinases which phosphorylate sites 2 and 3 in glycogen synthase and/or activate the Mg++/ATP-dependent protein phosphatase I. Effects of the insulin receptor tyrosine protein kinase on these serine/threonine protein kinases and phosphatases will be examined directly using purified enzymes as well as in situ in diaphragm and cultured cells. In the latter case a highly specific antiphosphotyrosine monoclonal antibody affinity column will be utilized to selectively purify protein kinases and phosphatases containing phosphotyrosine. Another approach will be to assess potential effects of insulin-generated """"""""modulator"""""""" molecules, derived from a phosphatidylinositol-glycan by activation of a specific phospholipase C, on these glycogen synthase protein kinases and phosphatases. Potential effects of insulin on the subcellular distribution of the protein kinase that activates the Mg /ATP- dependent phosphatase and on the phosphatase itself will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK017808-19
Application #
3225874
Study Section
Biochemistry Study Section (BIO)
Project Start
1978-07-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1994-06-30
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Type
Organized Research Units
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239