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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    84 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)775-783
    Number of pages9
    JournalJournal of Neurochemistry
    Issue number4
    Publication statusPublished - 1 Nov 2002


    • 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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