CHARACTERIZATION OF LIGAND-DEPENDENT PHOSPHORYLATION OF THE ESTROGEN-RECEPTOR

The mouse estrogen receptor is phosphorylated upon estrogen binding at multiple serine residues located mainly between residues 121 and 599. Phosphorylation is progessively reduced in mutant receptors that are defective in estrogen- and DNA-binding activities, suggesting that is occurs in stages, initially as a consequence of hormone binding and su bsequently after DNA binding. Phosphopeptide maps of the receptor expr essed in the presence of estrogen or 4-hydroxytamoxifen are similar, s uggesting that the effects of this antiestrogen of transcriptional act ivity are not mediated by differences in phosphorylation. Although it is unclear whether phosphorylation is a prerequisite for transcription al activity, the similarity in the phosphopeptide maps of the wild-typ e receptor and the transcriptionally defective mutant confirm that pho sphorylation does not occur simply as a consequence of estrogen-depend ent transcriptional activation.