Regulation of tyrosine hydroxylase by stress-activated protein kinases

Karen Toska; Rune Kleppe; Christopher G. Armstrong; Nick A. Morrice; Philip Cohen; Jan Haavik

doi:10.1046/j.1471-4159.2002.01172.x

Regulation of tyrosine hydroxylase by stress-activated protein kinases

Karen Toska, Rune Kleppe, Christopher G. Armstrong, Nick A. Morrice, Philip Cohen, Jan Haavik

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82 Citations (Scopus)

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 V_max and a decrease in K_m 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.

Original language	English
Pages (from-to)	775-783
Number of pages	9
Journal	Journal of Neurochemistry
Volume	83
Issue number	4
DOIs	https://doi.org/10.1046/j.1471-4159.2002.01172.x
Publication status	Published - 1 Nov 2002

Keywords

14-3-3 proteins
MSK1
PRAK
Stress-activated protein kinases
Tyrosine hydroxylase

ASJC Scopus subject areas

Biochemistry
Cellular and Molecular Neuroscience

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title = "Regulation of tyrosine hydroxylase by stress-activated protein kinases",

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.",

keywords = "14-3-3 proteins, MSK1, PRAK, Stress-activated protein kinases, Tyrosine hydroxylase",

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AU - Kleppe, Rune

AU - Armstrong, Christopher G.

AU - Morrice, Nick A.

AU - Cohen, Philip

AU - Haavik, Jan

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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.

AB - 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.

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Regulation of tyrosine hydroxylase by stress-activated protein kinases

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Keywords

ASJC Scopus subject areas

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