The aryl hydrocarbon receptor at the crossroads of multiple signaling pathways.

The aryl hydrocarbon receptor (AHR) has long been recognized as a ligand-activated transcription factor responsible for the induction of drug-metabolizing enzymes. Its role in the combinatorial matrix of cell functions was established long before the first report of an AHR cDNA sequence was published. It is only recently that other functions of this protein have begun to be recognized, and it is now clear that the AHR also functions in pathways outside of its well-characterized role in xenobiotic enzyme induction. Perturbation of these pathways by xenobiotic ligands may ultimately explain much of the toxicity of these compounds. This chapter focuses on the interactions of the AHR in pathways critical to cell cycle regulation, mitogen-activated protein kinase cascades, differentiation and apoptosis. Ultimately, the effect of a particular AHR ligand on the biology of the organism will depend on the milieu of critical pathways and proteins expressed in specific cells and tissues with which the AHR itself interacts.