Regulation of tyrosine hydroxylase by stress‐activated protein kinases

Recombinant human tyrosine hydroxylase (hTH1) was found to be phosphorylated by mitogen and stress‐activated protein kinase 1 (MSK1) at Ser40 and by p38 regulated/activated kinase (PRAK) on Ser19. Phosphorylation by MSK1 induced an increase in Vmax and a decrease in Km for 6‐(R)‐5,6,7,8‐tetrahydrobi...

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Bibliographic Details
Published in:Journal of neurochemistry 2002-11, Vol.83 (4), p.775-783
Main Authors: Toska, Karen, Kleppe, Rune, Armstrong, Christopher G., Morrice, Nick A., Cohen, Philip, Haavik, Jan
Format: Article
Language:English
Subjects:
14-3-3 Proteins
Amino Acid Sequence
Analytical, structural and metabolic biochemistry
Binding Sites
Biological and medical sciences
Chromatography, High Pressure Liquid
Circular Dichroism
Cyclic AMP-Dependent Protein Kinases - chemistry
Enzyme Activation - physiology
Enzyme Stability - physiology
Fundamental and applied biological sciences. Psychology
Humans
Intracellular Signaling Peptides and Proteins
Kinetics
Mitogen-Activated Protein Kinase 1 - chemistry
MSK1
Other biological molecules
Phosphorylation
PRAK
Protein Binding - physiology
Protein-Serine-Threonine Kinases - chemistry
Ribosomal Protein S6 Kinases, 90-kDa - chemistry
stress‐activated protein kinases
Substrate Specificity - physiology
Surface Plasmon Resonance
Temperature
Terpenes, steroids. Hormones
Tyrosine 3-Monooxygenase - chemistry
tyrosine hydroxylase
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Summary:Recombinant human tyrosine hydroxylase (hTH1) was found to be phosphorylated by mitogen and stress‐activated protein kinase 1 (MSK1) at Ser40 and by p38 regulated/activated kinase (PRAK) on Ser19. Phosphorylation by MSK1 induced an increase in Vmax and a decrease in Km for 6‐(R)‐5,6,7,8‐tetrahydrobiopterin (BH4), while these kinetic parameters were unaffected as a result of phosphorylation by PRAK. Phosphorylation of both Ser40 and Ser19 induced a high‐affinity binding of 14‐3‐3 proteins, but only the interaction of 14‐3‐3 with Ser19 increased the hTH1 activity. The 14‐3‐3 proteins also inhibited the rate of dephosphorylation of Ser19 and Ser40 by 82 and 36%, respectively. The phosphorylation of hTH1 on Ser19 caused a threefold increase in the rate of phosphorylation of Ser40. These studies provide new insights into the possible roles of stress‐activated protein kinases in the regulation of catecholamine biosynthesis.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.2002.01172.x