ArticleThe Journal of biological chemistry2011
Active ERK1/2 protein interacts with the phosphorylated nuclear constitutive active/androstane receptor (CAR; NR1I3), repressing dephosphorylation and sequestering CAR in the cytoplasm.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Yinchenhao decoction alleviates obstructive jaundice liver injury by modulating epidermal growth factor receptor and constitutive androstane receptor signaling.World journal of hepatology · 2025Article
- Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.Molecular metabolism · 2024Article
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Nuclear receptor phosphorylation in xenobiotic signal transduction.The Journal of biological chemistry · 2020Review
- NRF2-Independent Regulation of Intestinal Constitutive Androstane Receptor by the Pro-Oxidants Cadmium and Isothiocyanate inDrug metabolism and disposition: the biological fate of chemicals · 2020Article
- The Roles of Xenobiotic Receptors: Beyond Chemical Disposition.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Post-hepatectomy liver regeneration in the context of bile acid homeostasis and the gut-liver signaling axis.Journal of clinical and translational research · 2018Article
- Interaction of the phosphorylated DNA-binding domain in nuclear receptor CAR with its ligand-binding domain regulates CAR activation.The Journal of biological chemistry · 2018Article
- Teriflunomide Is an Indirect Human Constitutive Androstane Receptor (CAR) Activator Interacting With Epidermal Growth Factor (EGF) Signaling.Frontiers in pharmacology · 2018Article
- Multiple analyses indicate the specific association of NR1I3, C6 and TNN with low hip BMD risk.Journal of genetics and genomics = Yi chuan xue bao · 2017Article
- Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation.Molecular and cellular biology · 2017Article
- Phenobarbital Meets Phosphorylation of Nuclear Receptors.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Phosphorylation of Farnesoid X Receptor at Serine 154 Links Ligand Activation With Degradation.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk.Expert opinion on drug metabolism & toxicology · 2016Review
- Mechanisms of xenobiotic receptor activation: Direct vs. indirect.Biochimica et biophysica acta · 2016Review
- Nuclear receptors and nonalcoholic fatty liver disease.Biochimica et biophysica acta · 2016Review
- p38 MAP Kinase Links CAR Activation and Inactivation in the Nucleus via Phosphorylation at Threonine 38.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
- Phenobarbital and Insulin Reciprocate Activation of the Nuclear Receptor Constitutive Androstane Receptor through the Insulin Receptor.The Journal of pharmacology and experimental therapeutics · 2016Article
- The Use of the LanthaScreen TR-FRET CAR Coactivator Assay in the Characterization of Constitutive Androstane Receptor (CAR) Inverse Agonists.Sensors (Basel, Switzerland) · 2015Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The nuclear constitutive active/androstane receptor (CAR) is inactivated and sequestered in the cytoplasm when Thr-38 is phosphorylated. Here, we have demonstrated that activated ERK1/2 interacts with phosphorylated CAR to repress dephosphorylation of Thr-38. The phosphorylation-dependent interaction between CAR and ERK1/2 was examined by co-immunoprecipitation experiments of ectopically expressed FLAG-tagged CAR T38A and CAR T38D mutants with endogenous phospho-ERK1/2 in Huh-7 cells. Phospho-ERK1/2 coprecipitated only the phosphorylation-mimicking CAR T38D mutant; this coprecipitation was mediated by the interaction with the xenochemical response signal peptide near the C terminus of CAR. This interaction increased after EGF treatment and decreased after treatment with the MEK inhibitor U0126 as well as after knockdown of MEK1/2 by shRNA in Huh-7 cells. The phosphorylation levels of Thr-38 of CAR decreased in U0126-treated Huh-7 cells. Thus, activated ERK1/2 interacts with CAR and represses dephosphorylation of Thr-38, providing a cell signal-regulated mechanism for CAR activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.