title: Kinetics of regulatory serine variants of tyrosine hydroxylase with cyclic AMP-dependent protein kinase and extracellular signal-regulated protein kinase 2.
abstract: Rat tyrosine hydroxylase is phosphorylated at four serine residues, at positions 8, 19, 31, and 40 in its amino terminal regulatory domain by multiple protein kinases. Cyclic AMP-dependent protein kinase phosphorylates S40, which results in alleviation of inhibition by dopamine. Extracellular signal-regulated protein kinase 2 phosphorylates S8 and S31. Site-directed serine-to-glutamate mutations were introduced into tyrosine hydroxylase to mimic prior phosphorylation of the regulatory serines; these proteins were used as substrates for cAMP-dependent kinase and extracellular signal-regulated kinase 2. The activity of cAMP-dependent kinase was unaffected by the substitution of serines 8, 19 or 31 with glutamate and the activity of extracellular signal-regulated kinase 2 was unaffected by substitution of serines 19 or 40 with glutamate. Cyclic AMP-dependent kinase was less active in phosphorylating S40 if dopamine was bound to tyrosine hydroxylase, but extracellular signal-regulated kinase 2 phosphorylation at S31 was unaffected by the presence of dopamine.
authors.affiliation: Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Royo
authors.forename: S
authors.initials: S
authors.lastname: Colette Daubner
mesh_terms: D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*; D013379:Substrate Specificity; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1