MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on December 23, 2005; DOI: 10.1124/mol.105.019505

0026-895X/06/6904-1095-1102$20.00
Mol Pharmacol 69:1095-1102, 2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.105.019505v1
69/4/1095    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hosseinpour, F.
Right arrow Articles by Sueyoshi, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hosseinpour, F.
Right arrow Articles by Sueyoshi, T.
Original Article

Serine 202 Regulates the Nuclear Translocation of Constitutive Active/Androstane Receptor

F. Hosseinpour, R. Moore, M. Negishi, and T. Sueyoshi

Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina

Abstract

The constitutive active receptor (CAR) in mouse primary hepatocytes undergoes okadaic acid (OA)-sensitive nuclear translocation after activation by xenobiotics such as phenobarbital (PB) and 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). We have now mimicked this TCPOBOP-dependent and OA-sensitive translocation of mouse CAR (mCAR) in HepG2 cells and have demonstrated that protein phosphatase 2A regulates this nuclear translocation. Site-directed mutagenesis analysis of various Ser and Thr residues delineated the translocation activity to Ser-202. Mutation of Ser-202 to Asp (S202D) prevented mCAR translocation into the nucleus of TCPOBOP-treated HepG2 cells. In addition, in the livers of Car-/- mice, the YFP-tagged S202D mutant did not translocate into the nucleus after PB treatment. To examine whether Ser-202 can be phosphorylated, flag-tagged wild-type mCAR or flag-tagged S202A mutant was expressed in HepG2 cells and subjected to Western blot analysis using an antibody specific to a peptide containing phospho-Ser-202. A high molecular weight phosphorylated form of CAR was detected only with the wild-type mCAR. These results are consistent with the conclusion that the dephosphorylation of Ser-202 is a required step that regulates the xenobiotic-dependent nuclear translocation of mCAR.

Received October 4, 2005; accepted December 23, 2005

Address correspondence to: Dr. Masahiko Negishi, Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, NIH, Research Triangle Park, NC 2770. E-mail: negishi{at}niehs.nih.gov




This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
L. Li, T. Chen, J. D. Stanton, T. Sueyoshi, M. Negishi, and H. Wang
The Peripheral Benzodiazepine Receptor Ligand 1-(2-Chlorophenyl-methylpropyl)-3-isoquinoline-carboxamide Is a Novel Antagonist of Human Constitutive Androstane Receptor
Mol. Pharmacol., August 1, 2008; 74(2): 443 - 453.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
T. Sueyoshi, R. Moore, J. Sugatani, Y. Matsumura, and M. Negishi
PPP1R16A, The Membrane Subunit of Protein Phosphatase 1{beta}, Signals Nuclear Translocation of the Nuclear Receptor Constitutive Active/Androstane Receptor
Mol. Pharmacol., April 1, 2008; 73(4): 1113 - 1121.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Guo, J. Sarkar, K. Suino-Powell, Y. Xu, K. Matsumoto, Y. Jia, S. Yu, S. Khare, K. Haldar, M. S. Rao, et al.
Induction of Nuclear Translocation of Constitutive Androstane Receptor by Peroxisome Proliferator-activated Receptor {alpha} Synthetic Ligands in Mouse Liver
J. Biol. Chem., December 14, 2007; 282(50): 36766 - 36776.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. Xia and B. Kemper
Subcellular Trafficking Signals of Constitutive Androstane Receptor: Evidence for a Nuclear Export Signal in the DNA-Binding Domain
Drug Metab. Dispos., September 1, 2007; 35(9): 1489 - 1494.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. A. Stoner, S. S. Auerbach, S. M. Zamule, S. C. Strom, and C. J. Omiecinski
Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites
Nucleic Acids Res., April 1, 2007; 35(7): 2177 - 2190.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. M. Blattler, F. Rencurel, M. R. Kaufmann, and U. A. Meyer
In the regulation of cytochrome P450 genes, phenobarbital targets LKB1 for necessary activation of AMP-activated protein kinase
PNAS, January 16, 2007; 104(3): 1045 - 1050.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Ding, K. Lichti, I. Kim, F. J. Gonzalez, and J. L. Staudinger
Regulation of Constitutive Androstane Receptor and Its Target Genes by Fasting, cAMP, Hepatocyte Nuclear Factor {alpha}, and the Coactivator Peroxisome Proliferator-activated Receptor {gamma} Coactivator-1{alpha}
J. Biol. Chem., September 8, 2006; 281(36): 26540 - 26551.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics