Kuiper G G, Brinkmann A O
Department of Endocrinology and Reproduction, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Biochemistry. 1995 Feb 14;34(6):1851-7. doi: 10.1021/bi00006a005.
Phosphorylation of the androgen receptor (AR) in human prostate tumor cells (LNCaP) is increased by androgens. The AR is expressed as two isoforms with apparent molecular masses of 110 and 112 kDa. Metabolic labeling experiments with [32P]orthophosphate revealed that only the 112 kDa isoform is radioactively labeled. Phosphoamino acid analysis revealed only phosphorylation on serine residues. Phosphotryptic peptide analysis of human AR protein by two-dimensional peptide mapping and by reverse-phase HPLC showed phosphorylation at multiple sites. Comparison of phosphopeptide maps of AR protein from cells incubated in the absence or presence of the synthetic androgen R1881 indicated that the ligand-stimulated phosphorylation is probably due to induction of phosphorylation at a new site rather than increased phosphorylation at an existing site. This result suggests that hormone-dependent AR phosphorylation might play a role in the signal transduction pathway of androgens.
雄激素可增加人前列腺肿瘤细胞（LNCaP）中雄激素受体（AR）的磷酸化水平。AR以两种亚型形式表达，表观分子量分别为110 kDa和112 kDa。用[32P]正磷酸盐进行的代谢标记实验表明，只有112 kDa的亚型被放射性标记。磷酸氨基酸分析显示只有丝氨酸残基发生磷酸化。通过二维肽图和反相高效液相色谱对人AR蛋白进行磷酸化胰蛋白酶肽分析，结果表明多个位点发生了磷酸化。对在不存在或存在合成雄激素R1881的情况下培养的细胞中AR蛋白的磷酸肽图进行比较，结果表明，配体刺激的磷酸化可能是由于在一个新位点诱导了磷酸化，而不是在现有位点增加了磷酸化。这一结果表明，激素依赖性AR磷酸化可能在雄激素的信号转导途径中发挥作用。
