Regulation of DNA binding activity of the ligand-activated aryl hydrocarbon receptor by tyrosine phosphorylation.

Regulation of DNA binding activity of the ligand-activated aryl hydrocarbon receptor by tyrosine phosphorylation.
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通过酪氨酸磷酸化调节配体激活的芳烃受体的 DNA 结合活性。

DOI:
10.1006/abbi.2000.1999
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发表时间:
2000
影响因子:
3.9
通讯作者:
Gasiewicz,TA
Gasiewicz,TA
中科院分区:
生物学3区
文献类型:
--
作者:
Park,S;Henry,EC;Gasiewicz,TA

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芳香烃受体(AhR)是bHLH-PAS家族成员之一,是一种配体激活的转录因子,在调节多环和卤代芳香烃污染物如2,3,7,8-四氯二苯并-对二恶英的毒性中发挥重要作用。众所周知,磷酸化可以调节未连接的AhR向功能活性AhR/Arnt杂二聚体的转化过程,该杂二聚体与二恶英反应元件(DRE)具有高亲和力和反式激活活性。在这里,我们报告了AhR的DRE结合活性是由AhR/Arnt复合体本身的磷酸化调节的。对特定蛋白磷酸酶的研究表明,酪氨酸磷酸化参与了这种调节。此外,通过反酪氨酸免疫印迹分析确定AhR在酪氨酸残基(S)处被磷酸化。这些结果表明,AhR上的酪氨酸磷酸化是其DNA结合活性所必需的,并可能为哺乳动物细胞提供另一层控制机制,允许特定细胞类型和发育阶段特定的AhR靶基因的诱导。
Aryl hydrocarbon receptor (AhR), a member of the bHLH–PAS family, is a ligand-activated transcription factor which plays an important role in normal liver development and in mediating the toxicity of polycyclic and halogenated aromatic hydrocarbon pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Phosphorylation is known to regulate the transformation process of unliganded AhR into functionally active AhR/ARNT heterodimer that has high affinity for dioxin-responsive elements (DRE) and transactivation activity. Here, we report that DRE binding activity of the AhR is regulated by phosphorylation on the AhR/ARNT complex itself. Studies with specific protein phosphatases indicated that tyrosine phosphorylation is involved in this modulation. In addition, the AhR is phosphorylated at tyrosine residue(s) as determined by anti-phosphotyrosine immunoblot analysis. These results suggest that tyrosine phosphorylation on the AhR is required for its DNA binding activity and may provide mammalian cells with another layer of control mechanism that allows cell type specific and developmental stage specific induction of the AhR target genes.
大鼠胸腺中的一种抑制因子,干扰胞质 Ah 受体与异生素反应元件的结合。
DOI: --
发表时间: 1994
期刊: Biochemistry and molecular biology international
影响因子: --
作者:
Kurl,RN
通讯作者: Kurl,RN
2,3,7,8-四氯二苯并-对-二恶英 (TCDD) 对大鼠胸腺细胞中蛋白激酶 C 的刺激。
DOI: 10.1016/0378-4274(93)90142-k
发表时间: 1993
期刊: Toxicology letters
影响因子: 3.5
作者:
DePetrillo,PB;Kurl,RN
通讯作者: Kurl,RN
二恶英对细胞色素 P1-450 基因表达的控制。
DOI: 10.1126/science.3856321
发表时间: 1985
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Jones,PB;Galeazzi,DR;Fisher,JM;WhitlockJr,JP
通讯作者: WhitlockJr,JP
Ah 受体核转位蛋白异质性在与 Ah 受体异二聚化后发生改变。
DOI: 10.1021/bi970891w
发表时间: 1997
期刊: Biochemistry.
影响因子: --
作者:
Tsai,JC;Perdew,GH
通讯作者: Perdew,GH
DOI: --
发表时间: 1986
影响因子: 4.8
作者:
P. Jones;L. Durrin;J. Fisher;J. Whitlock
通讯作者: J. Whitlock