Abstract

We propose to continue our studies on the structure and function of enzymes involved in the regulating of carbohydrate metabolism in relation to hormone action and muscle contraction. Specifically, we are interested in: 1) The architecture of phosphorylase phosphatase, an enzyme that might play a central role in the control of glycogen synthesis and breakdown and the possible involvement of insulin in its regulation. The enzyme exists in an inactive form and the various mechanisms by which it can be activated are being investigated. 2) Crystallizing the cAMP-dependent protein kinase catalytic subunit and determining the structure and function of phosphorylase kinase with particular emphasis on the characterization of its catalytic sites and the role of its other subunits. 3) The structure and physiological function of a heat-stable protein inhibitor of protein kinase that has been isolated from skeletal muscle. A new project concerned with microtubule cold-stability has been initiated. Attempts are being made to isolate and characterize a number of microtubule-associated proteins involved in this process and to determine how their activity might be modulated by phosphorylation-dephosphorylation reactions catalyzed by calmodulin-dependent and independent kinases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM007902-23
Application #
3150737
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1978-09-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
23
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Stover, D R; Charbonneau, H; Tonks, N K et al. (1991) Protein-tyrosine-phosphatase CD45 is phosphorylated transiently on tyrosine upon activation of Jurkat T cells. Proc Natl Acad Sci U S A 88:7704-7
Tonks, N K; Diltz, C D; Fischer, E H (1990) CD45, an integral membrane protein tyrosine phosphatase. Characterization of enzyme activity. J Biol Chem 265:10674-80
Lerea, K M; Tonks, N K; Krebs, E G et al. (1989) Vanadate and molybdate increase tyrosine phosphorylation in a 50-kilodalton protein and stimulate secretion in electropermeabilized platelets. Biochemistry 28:9286-92
McNall, S J; Fischer, E H (1988) Phosphorylase phosphatase. Comparison of active forms using peptide substrates. J Biol Chem 263:1893-7
Tonks, N K; Diltz, C D; Fischer, E H (1988) Characterization of the major protein-tyrosine-phosphatases of human placenta. J Biol Chem 263:6731-7
Ledbetter, J A; Tonks, N K; Fischer, E H et al. (1988) CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells. Proc Natl Acad Sci U S A 85:8628-32
Tonks, N K; Diltz, C D; Fischer, E H (1988) Purification of the major protein-tyrosine-phosphatases of human placenta. J Biol Chem 263:6722-30
Charbonneau, H; Tonks, N K; Walsh, K A et al. (1988) The leukocyte common antigen (CD45): a putative receptor-linked protein tyrosine phosphatase. Proc Natl Acad Sci U S A 85:7182-6
Tonks, N K; Charbonneau, H; Diltz, C D et al. (1988) Demonstration that the leukocyte common antigen CD45 is a protein tyrosine phosphatase. Biochemistry 27:8695-701
Scott, J D; Glaccum, M B; Fischer, E H et al. (1986) Primary-structure requirements for inhibition by the heat-stable inhibitor of the cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 83:1613-6

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