Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins
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Amino Acid Sequence
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Binding Sites
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Chromatography, High Pressure Liquid
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Circular Dichroism
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Cyclic AMP-Dependent Protein Kinases / chemistry
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Enzyme Activation / physiology
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Enzyme Stability / physiology
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Humans
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Intracellular Signaling Peptides and Proteins
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Kinetics
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Mitogen-Activated Protein Kinase 1 / chemistry
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Phosphorylation
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Protein Binding / physiology
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Protein Serine-Threonine Kinases / chemistry*
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Ribosomal Protein S6 Kinases, 90-kDa / chemistry*
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Substrate Specificity / physiology
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Surface Plasmon Resonance
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Temperature
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Tyrosine 3-Monooxygenase / chemistry*
Substances
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14-3-3 Proteins
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Intracellular Signaling Peptides and Proteins
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MAP-kinase-activated kinase 5
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Tyrosine 3-Monooxygenase
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MAP-kinase-activated kinase 2
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases, 90-kDa
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mitogen and stress-activated protein kinase 1
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1