Numerous studies have established that a variety of endogenous neuroactive agents including the catecholamines and several neuropeptides are sulfated in vivo and that this reaction may play an essential role in regulating the physiological activity of these substances. There are a number of substrate specific sulfotransferases that are responsible for conjugation of these endogenous biologically active substances and as previously shown, these enzymes differ in their biochemical properties as well as their cellular and subcellular location. It is presently unclear as to contribution that each of the different forms of sulfotransferase play in this process. As previously demonstrated, the soluble sulfotransferase (M and P-PST) in human brain are biochemically distinct from that isolated from common laboratory animals thus, making it essential to characterize these sulfotransferases from human tissues. In this regard, the enzyme, tyrosylprotein sulfotransferase, which is responsible for the post- translational modification of neuropeptides such as cholecystokinin has not been characterized in human tissues including brain. Because of lack of information concerning these important regulatory enzymes the following specific studies are proposed: 1. Completion of our studies on the purification and preparation of antibodies for the different forms of human phenol sulfotransferase and on the immunohistochemical localization of these enzymes. 2. Isolate, purify and characterize the biochemical properties of human brain tyrosylprotein sulfotransferase (TPST) and prepare antibodies to this enzyme for immunohistochemical localization of the enzyme in human brain and other tissues. 3. Clone the genes for the different forms of human soluble (M and P-PST) and membrane-bound sulfotransferase (TPST).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020530-06
Application #
3400908
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1991-11-30
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Dentistry
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
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Lin, W H; Marcucci, K A; Rabin, R A et al. (1991) 2-Chloroadenosine decreases tyrosylprotein sulfotransferase activity in the Golgi apparatus in PC12 cells. Evidence for a novel receptor. J Biol Chem 266:14457-63
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Roth, J A; Grossman, M H; Adolf, M (1990) Variation in hepatic membrane-bound catechol-O-methyltransferase activity in Fischer and Wistar-Furth strains of rat. Biochem Pharmacol 40:1151-3
Lin, W H; Roth, J A (1990) Characterization of a tyrosylprotein sulfotransferase in human liver. Biochem Pharmacol 40:629-35
Zou, J Y; Petney, R; Roth, J A (1990) Immunohistochemical detection of phenol sulfotransferase-containing neurons in human brain. J Neurochem 55:1154-8
Heroux, J A; Falany, C N; Roth, J A (1989) Immunological characterization of human phenol sulfotransferase. Mol Pharmacol 36:29-33

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