Phosphorylation of serine-167 on the human oestrogen receptor is important for oestrogen response element binding and transcriptional activation.
We have studied the role of phosphorylation of the human oestrogen receptor (hOR; otherwise known as hER) at serine-167, which has been identified previously as the major oestrogen-induced phosphorylation site. We have tested transactivation by the hOR in yeast and cell-free transcription assays, and shown that mutation of serine-167 results in a 70% decrease in hOR-dependent transcription. Furthermore we explored the functional significance of phosphorylation at this site by hormone binding and DNA binding. DNA binding affinity was 10-fold lower when serine-167 was changed to alanine in the hOR. Cell-free transcription experiments showed that casein kinase II is the enzyme responsible for oestradiol-dependent phosphorylation of the hOR at serine-167. This suggests that a conformational change of the hOR must occur upon hormone binding that exposes serine-167 to casein kinase II, resulting in transactivation of oestrogen-responsive genes.
Castaño
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Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Vorojeikina
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DP
Notides
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D047390:Casein Kinase II; D002474:Cell-Free System; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012694:Serine / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D004967:Estrogens; D011960:Receptors, Estrogen; D012694:Serine; D004247:DNA; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases