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A ligand for the aryl hydrocarbon receptor isolated from lung

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dc.contributor.author Song, Jiasheng
dc.contributor.author Clagett-Dame, Margaret
dc.contributor.author Peterson, Richard E.
dc.contributor.author Hahn, Mark E.
dc.contributor.author Westler, William M.
dc.contributor.author Sicinski, Rafal R.
dc.contributor.author DeLuca, Hector F.
dc.date.accessioned 2006-04-20T12:51:17Z
dc.date.available 2006-04-20T12:51:17Z
dc.date.issued 2002-10-30
dc.identifier.citation Proceedings of the National Academy of Sciences 99 (2002): 14694-14699 en
dc.identifier.uri http://hdl.handle.net/1912/890
dc.description Author Posting. © National Academy of Sciences, 2002. This article is posted here by permission of National Academy of Sciences for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences 99 (2002): 14694-14699, doi:10.1073/pnas.232562899. en
dc.description.abstract The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is best known because it mediates the actions of polycyclic and halogenated aromatic hydrocarbon environmental toxicants such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We report here the successful identification of an endogenous ligand for this receptor; {approx}20 µg was isolated in pure form from 35 kg of porcine lung. Its structure was deduced as 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester from extensive physical measurements and quantum mechanical calculations. In a reporter gene assay, this ligand activates the AHR with a potency five times greater than that of {beta}-naphthoflavone, a prototypical synthetic AHR ligand. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester competes with 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin for binding to human, murine, and fish AHRs, thus showing that AHR activation is caused by direct receptor binding, and that recognition of this endogenous ligand is conserved from early vertebrates (fish) to humans. en
dc.description.sponsorship This work was supported by the Wisconsin Alumni Research Foundation, the University of Wisconsin Sea Grant Institute, and the National Institutes of Health. en
dc.format.extent 334887 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US en
dc.publisher National Academy of Sciences en
dc.relation.uri http://dx.doi.org/10.1073/pnas.232562899
dc.title A ligand for the aryl hydrocarbon receptor isolated from lung en
dc.type Article en
dc.identifier.doi 10.1073/pnas.232562899


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