Pongratz I, Strömstedt P E, Mason G G, Poellinger L
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Sweden.
J Biol Chem. 1991 Sep 5;266(25):16813-7.
The dioxin receptor stimulates transcription of the cytochrome P-450IA1 gene in response to dioxin. Exposure of the intracellular dioxin receptor to dioxin leads to a rapid conversion of the receptor from a latent form to a DNA binding species which specifically recognizes dioxin-responsive positive control elements in vitro. In this report, we show that treatment of in vivo or in vitro ligand-activated receptor with potato acid phosphatase significantly reduced or abolished its specific DNA binding activity. This effect was inhibited in the presence of sodium phosphate. In control experiments, the ligand-activated glucocorticoid receptor was not inactivated by phosphatase treatment. Moreover, phosphatase treatment did not induce any detectable degradation of covalently labeled dioxin receptor, arguing against protease contamination as a cause for receptor inactivation. Finally, phosphatase-inactivated dioxin receptor exhibited bona fide levels of ligand binding activity. Taken together, these data suggest that phosphorylation may regulate the DNA binding activity of the ligand-occupied dioxin receptor.
二噁英受体可响应二噁英刺激细胞色素P-450IA1基因的转录。细胞内的二噁英受体与二噁英接触后，会迅速从潜伏形式转变为一种能在体外特异性识别二噁英反应性阳性对照元件的DNA结合形式。在本报告中，我们表明用马铃薯酸性磷酸酶处理体内或体外的配体激活受体，会显著降低或消除其特异性DNA结合活性。在存在磷酸钠的情况下，这种效应受到抑制。在对照实验中，配体激活的糖皮质激素受体不会因磷酸酶处理而失活。此外，磷酸酶处理并未诱导共价标记的二噁英受体发生任何可检测到的降解，这排除了蛋白酶污染作为受体失活原因的可能性。最后，磷酸酶失活的二噁英受体表现出真正水平的配体结合活性。综上所述，这些数据表明磷酸化可能调节配体占据的二噁英受体的DNA结合活性。
