Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitro.
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.
Lechtken
Adriane
A
Institute of Pharmaceutical Chemistry/ZAFES, Johann Wolfgang Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
Hörnig
Michael
M
Werz
Oliver
O
Corvey
Nadine
N
Zündorf
Ilse
I
Dingermann
Theo
T
Brandes
Ralf
R
Steinhilber
Dieter
D
D000595:Amino Acid Sequence; D002940:Circadian Rhythm; D003001:Cloning, Molecular; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D013912:Threonine / Q000737:chemistry; D015534:Trans-Activators / Q000378:metabolism*
D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D013912:Threonine; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1