Specificity of the MAP kinase ERK2 for phosphorylation of tyrosine hydroxylase.
Short-term regulation of catecholamine biosynthesis involves reversible phosphorylation of several serine residues in the N-terminal regulatory domain of tyrosine hydroxylase. The MAP kinases ERK1/2 have been identified as responsible for phosphorylation of Ser31. As an initial step in elucidating the effects of phosphorylation of Ser31 on the structure and activity of tyrosine hydroxylase, the kinetics of phosphorylation of the rat enzyme by recombinant rat ERK2 have been characterized. Complete phosphorylation results in incorporation of 2mol of phosphate into each subunit of tyrosine hydroxylase. The S8A and S31A enzymes only incorporate a single phosphate, while the S19A and S40A enzymes incorporate two. Phosphorylation of S8A tyrosine hydroxylase is nine times as rapid as phosphorylation of the S31A enzyme, consistent with a ninefold preference of ERK2 for Ser31 over Ser8.
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA. fitzpat@tamu.edu
Montserrat
M
Royo
S Colette
SC
Daubner
Paul F
PF
Fitzpatrick
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
D010761:Phosphorus Radioisotopes; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1