Protein kinase A activates and phosphorylates RORα4 in vitro and takes part in RORα activation by CaMK-IV

• Published in: Biochemical and biophysical research communications 2011-05, Vol.408 (3), p.442-446
• Main Authors: Ermisch, Michael, Firla, Beate, Steinhilber, Dieter
• Format: Article
• Language: English
• Subjects: Calcium-Calmodulin-Dependent Protein Kinase Type 4 - metabolism; CaM kinase; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - genetics; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits - metabolism; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Glycogen - metabolism; HeLa Cells; Humans; Lipid Metabolism; Nuclear receptor; Nuclear Receptor Subfamily 1, Group F, Member 1 - agonists; Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics; Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism; Protein kinase A; RORα; Serine - genetics; Serine - metabolism; Substrate Specificity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.04.046

► RORα is activated by protein kinase A. ► Protein kinase A is involved in the stimulation of RORα by CaM kinase-IV. ► Protein kinase A phosphorylates RORα at ser99. 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.