Abstract

This application describes a comprehensive biochemical study of the regulation of calmodulin activity. Calmodulin, a calcium-binding protein, has been shown to mediate the calcium activation of many enzymes and physiological processes. Preliminary experiments have indicated that calmodulin undergoes two types of post-translational modification - N-methylation and carboxymethylation, which accompanies tardive dyskinesia, is related to an increase in membrane-bound calmodulin. We will investigate the N-methylation and carboxymethylation of calmodulin in an attempt to determine the functional sugnificance of these alterations in calmodulin structure. In other studies we will examine the regulation and enzymology of calmodulin regulation, the factors responsible for binding of calmodulin to neural membranes, and the factors which govern calmodulin biosynthesis and degradation. The effects of acute and chronic administration of neuroactive drugs affecting receptor sensitivity on these aspects of calmodulin modification, function and synthesis will be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS011652-11
Application #
3394547
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1978-05-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Siegel, F L (1988) Enzymatic N-methylation of calmodulin. Adv Exp Med Biol 231:341-51
Siegel, F L; Wright, L S; Rowe, P M (1987) Calmodulin as an activator and a substrate of methyltransferase enzymes. Methods Enzymol 139:667-77
Vincent, P L; Siegel, F L (1987) Carboxylmethylation of calmodulin in cultured pituitary cells. J Neurochem 49:1613-22
Rowe, P M; Wright, L S; Siegel, F L (1986) Calmodulin N-methyltransferase. Partial purification and characterization. J Biol Chem 261:7060-9
Gourley, G R; Arend, R; Mogilevsky, W S et al. (1986) Bilirubin conjugate excretion and bilirubin uridine diphosphoglucuronyltransferase activity in nonjaundiced homozygous and heterozygous Gunn rats. J Lab Clin Med 108:436-41
Murtaugh, T J; Wright, L S; Siegel, F L (1986) Posttranslational modification of calmodulin in rat brain and pituitary. J Neurochem 47:164-72
Roberts, D M; Rowe, P M; Siegel, F L et al. (1986) Trimethyllysine and protein function. Effect of methylation and mutagenesis of lysine 115 of calmodulin on NAD kinase activation. J Biol Chem 261:1491-4
Elliott, M E; Siegel, F L; Hadjokas, N E et al. (1985) Angiotensin effects on calcium and steroidogenesis in adrenal glomerulosa cells. Endocrinology 116:1051-9
Murtaugh, T J; Wright, L S; Siegel, F L (1985) Calmodulin plus cyclic AMP-dependent phosphorylation of a Mr 22,000 pituitary protein. J Biol Chem 260:15932-7
Gourley, G R; Mogilevsky, W; Arend, R A et al. (1985) Effects of anesthetic agents on bile pigment excretion in the rat. Hepatology 5:610-4

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