Tyrosine Hydroxylase: A Substrate of Cyclic AMP-Dependent Protein Kinase

Data demonstrating the direct phosphorylation of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] purified from rat pheochromocytoma by ATP, Mg2+, and cyclic AMP-dependent protein kinase catalytic subunit are prese...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1980-01, Vol.77 (1), p.92-96
Main Authors: Vulliet, P. R., Langan, T. A., Weiner, N.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Animals
Cells, Cultured
Cyclic AMP - metabolism
Enzyme Activation
Enzymes
Gels
Histones
Histones - metabolism
Kinetics
Neoplasms, Experimental - enzymology
Pheochromocytoma
Pheochromocytoma - enzymology
Phosphates
Phosphorylation
Potassium phosphates
Protein Kinases - metabolism
Pterins - metabolism
Rats
Sulfates
Tumors
Tyrosine 3-Monooxygenase - metabolism
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Summary:Data demonstrating the direct phosphorylation of tyrosine hydroxylase [tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] purified from rat pheochromocytoma by ATP, Mg2+, and cyclic AMP-dependent protein kinase catalytic subunit are presented. The incorporation of phosphate is highly correlated with the activation of the hydroxylase when either the time of preincubation or the amount of protein kinase subunit is varied. The rate of phosphorylation of tyrosine hydroxylase compares favorably with that of H1 histone, a known substrate of protein kinase. Lineweaver--Burk analysis of crude or purified rat pheochromocytoma tyrosine hydroxylase activity, as a function of pterin cofactor concentration, in the absence of ATP, Mg2+, and protein kinase catalytic subunit, yields a curvilinear relationship which can be resolved into two lines, suggesting two enzyme forms with different affinities for pterin cofactor. A fraction of the hydroxylase present in the tumor exists in the activated state, presumably due to the presence of ATP and endogenous protein kinase activity. When the soluble enzyme is activated by cyclic AMP, ATP, Mg2+, and protein kinase, virtually all of the enzyme is converted to the low Kmstate. We conclude that tyrosine hydroxylase is a substrate of cyclic AMP-dependent protein kinase in vitro and, presumably, in vivo.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.77.1.92