title: Ca2+ -dependent activation of tyrosine hydroxylase involves MEK1.
abstract: Tyrosine hydroxylase (TOH) activity is regulated acutely by phosphorylation of serines 8, 19, 31 and 40. The only kinases known to phosphorylate Ser31 are the mitogen-activated protein kinases MAPK-1 and 2. The involvement of these kinases in TOH activation in situ was therefore investigated using intact bovine chromaffin cells. Nicotine, K+ and A23187 increased TOH activity over 10 min in a Ca2+-dependent manner. The response to all three was reduced by PD098059, a selective inhibitor of the upstream activator of MAPK, MEK1. In contrast, TOH activation by forskolin and phorbol dibutyrate were unaffected by PD098059. The results support a key role for MEK1/MAPK in the acute activation of TOH by nicotinic receptors and by other agonists that increase cytosolic Ca2+.
authors.affiliation: Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Griffiths
authors.forename: P D
authors.initials: PD
authors.lastname: Marley
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D048369:MAP Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007476:Ionophores; D018722:Nicotinic Agonists; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D011188:Potassium; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium