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Epidermal Growth Factor Receptor: The Phenobarbital Receptor that Elicits CAR Activation Signal for P450 Induction

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Fifty Years of Cytochrome P450 Research

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Abstract

Phenobarbital is the classic inducer of cytochrome P450 and drug metabolism. Here we describe the cell signaling mechanism by which phenobarbital binds to antagonize epidermal growth factor receptor to indirectly activate the nuclear constitutive androstane receptor (CAR). In response to this signaling, residue threonine 38 of CAR is dephosphorylated in the cytoplasm. Nonphosphorylated CAR translocates into the nucleus, thereby activating genes that encode enzymes and transporters to induce drug metabolism and excretion.

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Acknowledgments

This research was supported by the Intramural Research Program of National Institute of Environmental Health Sciences (Grants Z01ES1005-01).

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Authors and Affiliations

  1. Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA

    Shingo Mutoh & Masahiko Negishi

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  1. Shingo Mutoh
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  2. Masahiko Negishi
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Correspondence to Masahiko Negishi .

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Editors and Affiliations

  1. Showa Pharmaceutical University, Tokyo, Japan

    Hiroshi Yamazaki

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Mutoh, S., Negishi, M. (2014). Epidermal Growth Factor Receptor: The Phenobarbital Receptor that Elicits CAR Activation Signal for P450 Induction. In: Yamazaki, H. (eds) Fifty Years of Cytochrome P450 Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54992-5_14

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