The SMRT corepressor is a target of phosphorylation by protein kinase CK2 (casein kinase II)

The Silencing-Mediator for Retinoid/Thyroid hormone receptors (SMRT) intera cts with, and mediates transcriptional repression by, a variety of eukaryot ic transcription factors, including the nuclear hormone receptors. The abil ity of SMRT to function as a transcriptional 'corepressor' is regulated by a variety of signal transduction pathways. We report here that SMRT is a ph osphoprotein in vivo, and is also phosphorylated in vitro by unfractionated cell extracts. A major site of phosphorylation of SMRT is a protein kinase CK2 motif centered on serine 1492, and located within a C-terminal SMRT do main that mediates interaction of the corepressor with the nuclear hormone receptors. Phosphorylation of SMRT by CK2 stabilizes the ability of the SMR T protein to interact with nuclear hormone receptors. Our results indicate that SMRT is a member of an expanding family of transcriptional regulators that are modified, and potentially regulated, in response to protein kinase CK2.