The AH Receptor of the Most Dioxin-Sensitive Species, Guinea Pig, Is Highly Homologous to the Human AH Receptor

Korkalainen, Merja; Tuomisto, Jouko; Pohjanvirta, Raimo

doi:10.1006/bbrc.2001.5317

Cited by 41 publications

(26 citation statements)

References 35 publications

(40 reference statements)

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“…Substitutions in the basic domain alter DNA binding activity (44). Differences in sensitivity to TCDD toxicity among rodent species have been attributed to differences in the C-terminal sequences of the respective AHRs (45,46). Our results are significant, because they identify a part of the AHR protein that appears to play a role in the ligand-regulated interactions between these previously identified domains.…”

Section: Resultsmentioning

confidence: 66%

Identification of a Critical Amino Acid in the Aryl Hydrocarbon Receptor

Andreasen

Tanguay

Peterson

et al. 2002

Journal of Biological Chemistry

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Two aryl hydrocarbon receptors (rtAHR2␣ and rtAHR2␤) have been identified in the rainbow trout (Oncorhynchus mykiss). These receptors share 98% amino acid identity, yet their functional properties differ. Both rtAHR2␣ and rtAHR2␤ bind 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD), dimerize with rainbow trout ARNTb (rtARNTb), and recognize dioxin response elements in vitro. However, in a transient transfection assay the two proteins show differential ability to recognize enhancers, produce transactivation, and respond to TCDD. To identify the sequence differences that confer the functional differences between rtAHR2␣ and rtAHR2␤, we constructed chimeric rtAHRs, in which segments of one receptor form was replaced with the corresponding part from the other isoform. This approach progressively narrowed the region being examined to a single residue, corresponding to position 111 in rtAHR2␤. Altering this residue in rtAHR2␤ from the lysine to glutamate found in rtAHR2␣ produced an rtAHR2␤ with the properties of rtAHR2␣. All other known AHRs resemble rtAHR2␣ and carry glutamate at this position, located at the N terminus of the PAS-A domain. We tested the effect of altering this glutamate in the human and zebrafish AHRs to lysine. This lysine substitution produced AHRs with transactivation properties that were similar to rtAHR2␤. These results identify a critical residue in AHR proteins that has an important impact on transactivation, enhancer site recognition, and regulation by ligand.

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Section: Resultsmentioning

confidence: 66%

Identification of a Critical Amino Acid in the Aryl Hydrocarbon Receptor

Andreasen

Tanguay

Peterson

et al. 2002

Journal of Biological Chemistry

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“…Recently, it has been reported that the guinea pig Ah receptor is the closest homolog to the human Ah receptor. 8) This report emphasizes the danger for humans of exposure to dioxins. Dioxins are extremely toxic and accumulate within the food chain due to their high lipophilicity and stability.…”

mentioning

confidence: 91%

Distribution of PCDDs/PCDFs and Co-PCBs in Human Maternal Blood, Cord Blood, Placenta, Milk, and Adipose Tissue: Dioxins Showing High Toxic Equivalency Factor Accumulate in the Placenta

Suzuki

Nakano

Nakano³

2005

Bioscience, Biotechnology, and Biochemistry

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“…The dissociation constant (K d ) of hAHR for TCDD was comparable to that of TCDD-resistant DBA͞2 AHR (9,19), suggesting that humans might be resistant to TCDD. By contrast, high homology of the human receptor to the AHR of the guinea pig, which is the most sensitive animal to TCDD, suggests a high responsiveness of humans to the toxin (20). Ligand specificity of hAHR was also examined and compared with those of zebrafish and rainbow trout AHRs using polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners as test ligands.…”

mentioning

confidence: 99%