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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway. Karen.toska@ibmb.uib.no
authors.forename: Karen
authors.initials: K
authors.lastname: Toska
authors.forename: Rune
authors.initials: R
authors.lastname: Kleppe
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Armstrong
authors.forename: Nick A
authors.initials: NA
authors.lastname: Morrice
authors.forename: Philip
authors.initials: P
authors.lastname: Cohen
authors.forename: Jan
authors.initials: J
authors.lastname: Haavik
mesh_terms: D048948:14-3-3 Proteins; D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry; D004789:Enzyme Activation / Q000502:physiology; D004795:Enzyme Stability / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000737:chemistry*; D013379:Substrate Specificity / Q000502:physiology; D020349:Surface Plasmon Resonance; D013696:Temperature; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry*; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D048948:14-3-3 Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D047908:Intracellular Signaling Peptides and Proteins; D019950:Mitogen-Activated Protein Kinase 1; D017346:Protein Serine-Threonine Kinases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D014446:Tyrosine 3-Monooxygenase; D000099190:MAP-Kinase-Activated Kinase 2; C111049:MAP-kinase-activated kinase 5; C116919:mitogen and stress-activated protein kinase 1