The role of phosphorylation in human estrogen receptor function.
We have studied the role of phosphorylation of the human estrogen receptor (hER) at serine 118, which has been previously identified as a site important for transactivation. We have tested this transactivation in yeast and cell-free transcription assays, and have shown that mutation of serine 118 to alanine results in a 30-40% decrease in hER-dependent transcription. Furthermore, we investigated the functional significance of phosphorylation at this site by hormone binding and DNA binding. The mutation of serine 118 to alanine in the hER caused no decrease in its affinity for either estradiol or an ERE. The mutant receptor had an altered phosphorylation pattern when expressed in COS-1 and Sf9 cells, but not in HeLa cells. Our findings indicate that phosphorylation of serine 118 of the hER plays a role in regulating its transcriptional activity.
Department MCB, Harvard University, Cambridge, MA 02138, USA. ecastano@fas.harvard.edu
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Castaño
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Chen
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Vorojeikina
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Notides
D002474:Cell-Free System; D004958:Estradiol / Q000378:metabolism; D006801:Humans; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000235:genetics; D015533:Transcriptional Activation
D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D012694:Serine; D004958:Estradiol