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PMID:9111057

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Citation

Carver, LA and Bradfield, CA (1997) Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo. J. Biol. Chem. 272:11452-6

Abstract

In an effort to identify regulators of aryl hydrocarbon receptor (AHR) signaling, we have employed the yeast two-hybrid system to screen for human proteins that interact in a ligand-dependent manner with the AHR. After screening 1.4 x 10(6) clones from a human B cell library, two distinct clones were identified that associated specifically with the liganded receptor. No clones were identified that interacted preferentially with the unliganded AHR. One of the ligand-dependent clones, ARA9, encodes a novel 330-amino acid protein with regions of amino acid sequence similarity to the 52-kDa FK506-binding protein known to be associated with the glucocorticoid receptor. Yeast two-hybrid experiments with ARA9 demonstrated a strong interaction with the AHR that is enhanced 11-fold in the presence of the ligand beta-naphthoflavone. In vitro experiments using proteins generated in reticulocyte lysates confirmed this interaction and indicated that ARA9 can be co-immunoprecipitated with the AHR using antisera raised specifically for either the AHR or the 90-kDa heat shock protein. The observation that ARA9 has a high affinity for both the 90-kDa heat shock protein-associated and ligand-activated forms of the AHR suggests that ARA9 is a component of the AHR-signaling pathway in vivo.

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PubMed

Keywords

Amino Acid Sequence; Aryl Hydrocarbon Receptor Nuclear Translocator; B-Lymphocytes/metabolism; Base Sequence; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cloning, Molecular; DNA, Complementary/genetics; DNA-Binding Proteins/genetics; Heat-Shock Proteins/genetics; Humans; Intracellular Signaling Peptides and Proteins; Ligands; Molecular Sequence Data; Nuclear Proteins; Protein Binding; Proteins; Receptors, Aryl Hydrocarbon/agonists; Receptors, Aryl Hydrocarbon/metabolism; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Signal Transduction; Tacrolimus Binding Proteins; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


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