Protein kinase A activates and phosphorylates RORalpha4 in vitro and takes part in RORalpha activation by CaMK-IV.

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Ermisch M, Firla B, Steinhilber D

Protein kinase A activates and phosphorylates RORalpha4 in vitro and takes part in RORalpha activation by CaMK-IV.

Biochem Biophys Res Commun. 2011 May 13;408(3):442-6. doi: 10.1016/j.bbrc.2011.04.046. Epub 2011 Apr 13.

PubMed ID
21514275 [ View in PubMed
]
Abstract

The retinoic acid related orphan receptor RORalpha 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 RORalpha4 phosphorylating kinase in vitro. The primary sequence of RORalpha4 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 RORalpha4 phosphorylation by PKA. Activation of PKA by dBcAMP results in a marked induction of RORalpha4 activity. Inhibition of PKA with the selective kinase inhibitor H89 inhibits dBcAMP mediated as well as CaMK-IV triggered increase in RORalpha4 transcriptional activity. The regulation of RORalpha 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.

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Polypeptides
NameUniProt ID
cAMP-dependent protein kinase catalytic subunit alphaP17612Details