Abstract
Tyrosine hydroxylase (TH, EC 1.14.16.2) catalyzes the first and rate-limiting step in the biosynthesis of catecholamines. Apart from tyrosine, the reaction requires dioxygen and the cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH4). Feedback inhibition by catecholamines, cofactor availability and serine phosphorylation are considered to be important post-translational regulatory mechanisms of TH activity (1). The human TH isoforms (hTHl-4) can be phosphorylated on Serl9, 31 and 40 by a range of different kinases. Phosphorylation at Ser40 by cAMP dependent protein kinase (PKA) has been shown to increase the inhibitory constant of catecholamines, lower the Km for BH4 and increase Vmax of the enzyme, whereas phosphorylation by Ca2+/calmodulin dependent protein kinase II (CaMKU) enables binding of 14-3-3 proteins and activation (Vmax) (2, 3).
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References
Kumer S.C., Vrana K.E. Intricate regulation of tyrosine hydroxylase activity and gene expression. J. Neurochem. 67: 443–462, 1996
Almås B., Le Bourdelles B., Flatmark T., Mallet J., Haavik J. Regulation of recombinant human tyrosine hydroxylase isozymes by catecholamine binding and phosphorylation. Structure/activity studies and mechanistic implications. Eur. J. Biochem. 209: 249–255, 1992
Ichimura T., Isobe T., Okuyama T., Yamauchi T., Fujisawa H. Brain 14-3-3 protein is an activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+, calmodulin-dependent protein kinase II. FEBS Lett. 219: 79–82, 1987
Kleppe R., Toska K., and Haavik J. Interaction of phosphorylated tyrosine hydroxylase with 14-3-3 proteins: evidence for a phosphoserine 40-dependent association. J. Neurochem. 77: 1097–1107, 2001
Sutherland C, Alterio J., Campbell D.G., Le Bourdelles B., Mallet J., Haavik J., Cohen P. Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2. Eur. J. Biochem. 217: 715–722, 1993
Le Bourdelles B., Horellou P., Le Caer J.P., Denefle P., Latta M., Haavik J., Guibert B., Mayaux J.F., Mallet J. Phosphorylation of human recombinant tyrosine hydroxylase isoforms 1 and 2: an additional phosphorylated residue in isoform 2, generated through alternative splicing. J. Biol. Chem. 266: 17124–17130, 1991
Itagaki C, Isobe T., Taoka M., Natsume T., Nomura N., Horigome T., Omata S., Ichinose R, Nagatsu T., Greene LA, Ichimura T. Stimulus-coupled interaction of tyrosine hydroxylase with 14-3-3 proteins. Biochemistry 38: 15673–15680, 1999
Haavik J., Le Bourdelles B., Martinez A., Flatmark T., Mallet J. Recombinant human tyrosine hydroxylase isozymes. Reconstitution with iron and inhibitory effect of other metal ions. Eur. J. Biochem. 199: 371–378, 1991
Toska K., Kleppe R., Haavik J. Mechanisms of tyrosine hydroxylase activation by stress activated protein kinases. Proceedings of the 12th International Symposium on the Chemistry and Biology of Pteridines and Folates, this volume
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Kleppe, R., Toska, K., Haavik, J. (2002). Interaction of Phosphorylated Tyrosine Hydroxylase with 14-3-3 Proteins: Effects on Phosphorylation Kinetics. In: Milstien, S., Kapatos, G., Levine, R.A., Shane, B. (eds) Chemistry and Biology of Pteridines and Folates. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0945-5_14
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DOI: https://doi.org/10.1007/978-1-4615-0945-5_14
Publisher Name: Springer, Boston, MA
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