Abstract |
Involvement of Ca2+/ calmodulin-dependent protein kinase II (Ca2+/ CaM-kinase II) on the phosphorylation of tyrosine hydroxylase (TH, EC.1.14.16.2) in rat pheochromocytoma, PC12h cells was examined using KN-62, 1-[N,O-Bis(5-isoquinolinsulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipe razine, a selective inhibitor of Ca2+/ CaM-kinase II. Both the enhanced phosphorylation of TH and the activated L-3,4-dihydroxyphenylalanine ( DOPA) formation in the high K+ depolarization were inhibited by 10 microM KN-62. After incubation of PC12h cells with 10 microM KN-62 for 1 hr, the activation of TH with 3 min incubation of 56 mM K+ was reduced to the basal activity. However, KN-62 did not directly affect the activity of purified rat TH at pH 6.0 or 7.0. These results indicate that Ca2+/ CaM-kinase II phosphorylates and activates TH of PC12h cells in the high K+ depolarization.
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Authors | A Ishii, K Kiuchi, R Kobayashi, M Sumi, H Hidaka, T Nagatsu |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 176
Issue 3
Pg. 1051-6
(May 15 1991)
ISSN: 0006-291X [Print] United States |
PMID | 1674865
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Isoquinolines
- Piperazines
- Protein Kinase Inhibitors
- Dihydroxyphenylalanine
- KN 62
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
- Tyrosine 3-Monooxygenase
- Calcium-Calmodulin-Dependent Protein Kinases
- Potassium
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Topics |
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
(analogs & derivatives)
- Adrenal Gland Neoplasms
- Animals
- Calcium-Calmodulin-Dependent Protein Kinases
- Cell Line
- Dihydroxyphenylalanine
(metabolism)
- Enzyme Activation
- Isoquinolines
(pharmacology)
- Kinetics
- Molecular Weight
- Pheochromocytoma
- Phosphorylation
- Piperazines
(pharmacology)
- Potassium
(pharmacology)
- Protein Kinase Inhibitors
- Rats
- Tyrosine 3-Monooxygenase
(isolation & purification, metabolism)
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