Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function

Retinoid X Receptor alpha (RXRalpha), a member of the steroid-thyroid hormone receptor super family, is phosphorylated in vitro by protein kinase A (PKA) and this phosphorylation is inhibited in presence of PKA inhibitory peptide. Analysis of various deletion mutants of RXRalpha indicate that the amino-terminal A/B domain is the target for PKA phosphorylation. An RXRalpha mutant in which serine residue 27 is mutated to alanine is no longer phosphorylated by PKA. In vivo transfection experiments in COS cells indicate that cyclic AMP represses retinoic acid-mediated transcriptional activation of RXRalpha and this repression is mediated by serine 27. These results indicate that serine 27 of RXRalpha is an unique target for phosphorylation by PKA in vitro and it has an important role in the crosstalk between RXRalpha and cyclic AMP signalling pathways.