Regulation of DNA binding activity of the ligand-activated aryl hydrocarbon receptor by tyrosine phosphorylation.
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.
Park
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Department of Environmental Medicine, School of Medicine, University of Rochester, New York 14642, USA.
Henry
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Gasiewicz
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D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D066298:In Vitro Techniques; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism*
C497398:ARNT protein, rat; C497397:Arnt protein, mouse; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D011994:Recombinant Proteins; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D014443:Tyrosine; D004247:DNA