title: TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors.
abstract: The TAO (for thousand-and-one amino acids) protein kinases activate p38 mitogen-activated protein (MAP) kinase cascades in vitro and in cells by phosphorylating the MAP/ERK kinases (MEKs) 3 and 6. We found that TAO2 activity was increased by carbachol and that carbachol and the heterotrimeric G protein Galphao could activate p38 in 293 cells. Using dominant interfering kinase mutants, we found that MEKs 3 and 6 and TAOs were required for p38 activation by carbachol or the constitutively active mutant GalphaoQ205L. To explore events downstream of TAOs, the effects of TAO2 on ternary complex factors (TCFs) were investigated. Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1. Reporter activity was reduced by the p38-selective inhibitor SB203580. Taken together, these studies suggest that TAO protein kinases relay signals from carbachol through heterotrimeric G proteins to the p38 MAP kinase, which then activates TCFs in the nucleus.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Malavika
authors.initials: M
authors.lastname: Raman
authors.forename: Linda
authors.initials: L
authors.lastname: Chen
authors.forename: Sheu Fen
authors.initials: SF
authors.lastname: Lee
authors.forename: Alfred G
authors.initials: AG
authors.lastname: Gilman
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D019943:Amino Acid Substitution; D002217:Carbachol / Q000494:pharmacology*; D002460:Cell Line; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D046911:Macromolecular Substances; D010446:Peptide Fragments; D011994:Recombinant Proteins; D002217:Carbachol; D017346:Protein Serine-Threonine Kinases; C122016:Taok2 protein, rat; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D020962:Heterotrimeric GTP-Binding Proteins