Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo.

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.
Mesh Terms:
Amino Acid Sequence, Aryl Hydrocarbon Receptor Nuclear Translocator, B-Lymphocytes, Base Sequence, Carrier Proteins, Cloning, Molecular, DNA, Complementary, DNA-Binding Proteins, Heat-Shock Proteins, Humans, Intracellular Signaling Peptides and Proteins, Ligands, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Proteins, Receptors, Aryl Hydrocarbon, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Signal Transduction, Tacrolimus Binding Proteins, Transcription Factors
J. Biol. Chem.
Date: Apr. 25, 1997
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