Ali S, Metzger D, Bornert J M, Chambon P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculte de Médicine, Strasbourg, France.
EMBO J. 1993 Mar;12(3):1153-60. doi: 10.1002/j.1460-2075.1993.tb05756.x.
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.
利用瞬时共转染系统，我们发现人雌激素受体（hER）在雌二醇（E2）存在时以及抗雌激素4-羟基他莫昔芬（OHT）和ICI 164,384（ICI）存在时都会发生磷酸化，尽管其效率低于E2。hER存在多个磷酸化位点；通过缺失和点突变，其中一个位点已定位在N端A/B区域的丝氨酸118处。在多种细胞类型中，将该丝氨酸突变为丙氨酸会导致hER对含有雌激素反应元件（ERE）的报告基因的转录激活显著降低，但不影响hER的DNA结合特性或核定位。因此，丝氨酸118的磷酸化对于位于雌激素受体A/B区域的转录激活功能1（AF-1）的作用很重要。
