title: Protein kinase A activates and phosphorylates RORα4 in vitro and takes part in RORα activation by CaMK-IV.
abstract: The retinoic acid related orphan receptor RORα positively regulates the transcription of genes important for cerebellar development, immune function, lipid metabolism, and circadian rhythm. In the present study, we identified protein kinase A (PKA) as RORα4 phosphorylating kinase in vitro. The primary sequence of RORα4 contains a PKA recognition motif (R-D-S99) within the c-terminal extension of the DNA-binding domain, and mutation of Ser-99 to Ala prevents RORα4 phosphorylation by PKA. Activation of PKA by dBcAMP results in a marked induction of RORα4 activity. Inhibition of PKA with the selective kinase inhibitor H89 inhibits dBcAMP mediated as well as CaMK-IV triggered increase in RORα4 transcriptional activity. The regulation of RORα activity by PKA as well as CaMK-IV provides a new link in the signalling network that regulates metabolic processes such as glycogen and lipid metabolism.
authors.affiliation: Institute for Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ermisch
authors.forename: Beate
authors.initials: B
authors.lastname: Firla
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
mesh_terms: D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000378:metabolism*; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D012694:Serine; D006003:Glycogen; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; D017868:Cyclic AMP-Dependent Protein Kinases; C517757:PRKACA protein, human; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4