Modulation of transcriptional activation by ligand-dependent phosphorylation of the human oestrogen receptor A/B region

EMBO J. 1993 Mar;12(3):1153-60.


Using a transient co-transfection system, we show that the human oestrogen receptor (hER) becomes phosphorylated in the presence of oestradiol (E2) as well as in the presence of the anti-oestrogens 4-hydroxy-tamoxifen (OHT) and ICI 164, 384 (ICI), although at lower efficiencies than with E2. There are multiple sites of phosphorylation in hER; using deletion and point mutants one of these sites has been mapped in the N-terminal A/B region at serine 118. Mutation of this serine to alanine caused, in a number of cell types, a significant reduction in transcriptional activation by hER from reporter genes containing an oestrogen response element (ERE), but did not affect the DNA binding properties or nuclear localization of hER. Thus phosphorylation of serine 118 is important for the action of the transcription activation function 1 (AF-1) located in the A/B region of the oestrogen receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / genetics
  • Estradiol / analogs & derivatives
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Point Mutation
  • Polyunsaturated Alkamides
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Sequence Deletion
  • Serine / metabolism
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology
  • Transcription, Genetic*


  • Estrogen Antagonists
  • Ligands
  • Polyunsaturated Alkamides
  • Receptors, Estrogen
  • Tamoxifen
  • afimoxifene
  • Serine
  • Estradiol
  • ICI 164384
  • Chloramphenicol O-Acetyltransferase