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Activation of orphan receptor‐mediated transcription by Ca 2+ /calmodulin‐dependent protein kinase IV
Author(s) -
Kane Christopher D.,
Means Anthony R.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.4.691
Subject(s) - neuron derived orphan receptor 1 , orphan receptor , transactivation , estrogen related receptor gamma , nuclear receptor , calmodulin , transcription factor , microbiology and biotechnology , biology , chemistry , biochemistry , gene , enzyme
Retinoid‐related receptor α (RORα) is an orphan nuclear receptor that constitutively activates transcription from its cognate response element. We show that RORα is Ca 2+ responsive, and a Ca 2+ /calmodulin‐independent form of Ca 2+ /calmodulin‐dependent protein kinase IV (CaMKIV) potentiates RORα‐dependent transcription 20‐ to 30‐fold. Other orphan receptors including RORα2, RORγ and COUP‐TFI are also potentiated by CaMKIV. Transcriptional activation by CaMKIV is orphan receptor selective and does not occur with either the thyroid hormone or estrogen receptor. CaMKIV does not phosphorylate RORα or its ligand‐binding domain (LBD) in vitro , although the LBD is essential for transactivation. Therefore, the RORα LBD was used in the mammalian two‐hybrid assay to identify a single class of small peptide molecules containing LXXLL motifs that interacted with greater affinity in the presence of CaMKIV. This class of peptides antagonized activation of orphan receptor‐mediated transcription by CaMKIV. These studies demonstrate a pivotal role for CaMKIV in the regulation of orphan receptor‐mediated transcription.