title: Peptide substrates for ERK1/2: structure-function studies of serine 31 in tyrosine hydroxylase.
abstract: The first physiological substrate identified for the extracellular signal-regulated protein kinases (ERKs) is serine 31 in tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. In the present studies, several synthetic peptides modeled after Ser31 in TH were evaluated as in vitro substrates for the ERKs. The phosphorylation of Ser31-containing peptides from type 1 human TH by activated, recombinant ERK2 was found to exhibit catalytic efficiencies (V(max)/K(m)) up to 4-fold higher than that of a synthetic myelin basic protein (MBP)-based peptide. Both types of peptides were also tested using extracts from PC12 cells (untreated or treated with nerve growth factor (NGF)). Although, the phosphorylation of the MBP peptide by extracts of PC12 cells was higher than that of the Ser31 peptide, the relative treatment-dependent increase was much greater for the Ser31 peptide and more closely mimicked the pattern of ERK phosphorylation, suggesting that the latter peptide may be a more specific substrate for the ERKs.
authors: Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, 1100-Florida Avenue, New Orleans, LA 70119, USA. jhayco@lsuhsc.edu
authors: John W
authors: JW
authors: Haycock
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry* / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism; D016716:PC12 Cells; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D012694:Serine / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D010455:Peptides; D012694:Serine; D014446:Tyrosine 3-Monooxygenase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases