Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro.
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Lechtken A, Hornig M, Werz O, Corvey N, Zundorf I, Dingermann T, Brandes R, Steinhilber D
Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):890-6. Epub 2007 May 11.
- PubMed ID
- 17512500 [ View in PubMed]
- Abstract
The retinoic acid related orphan receptor RORalpha activates transcription of genes that play an important role in cerebellar development, the protection against age-related degenerative processes, the regulation of inflammatory responses, and is one of the pivotal participants that control the circadian rhythmicity in the core-clock of mammals. We identified the extracellular signal-regulated kinase 2 (ERK-2) as RORalpha4 phosphorylating kinase in vitro. The primary sequence of RORalpha4 contains an ERK-2 recognition motif (P-L-T(128)-P) within the hinge domain, and mutation of Thr-128 to Ala prevents RORalpha4 phosphorylation by ERK. The RORalpha4-T128A mutant exhibits an increased DNA-binding affinity, an increased transcriptional activity and, in the interplay with the opponent RevErbalpha, acts as a stronger competitor at ROR response elements than RORalpha4-WT.