title: Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which plays a role as an intracellular mediator of the xenobiotic signaling pathway. We previously identified the minimum nuclear localization signal (NLS) of AhR(13-39): it is composed of two basic amino acid segments, AhR(13-16:RKRR) and AhR(37-39:KRH). In this study, we showed that the two protein kinase C (PKC) sites of Ser-12 and Ser-36 are located one amino acid upstream from each of the two segments, and that a ligand-dependent nuclear import of AhR is inhibited by substitution of aspartic acid for Ser-12 (S12D) or Ser-36 (S36D), which mimics the negative charge of phosphorylation. This observation was supported by microinjection analysis, an in vitro nuclear transport assay, and a luciferase reporter assay, suggesting a two-step mechanism in the ligand-dependent nuclear translocation of AhR.
authors.affiliation: Research Institute, Saitama Cancer Center, Saitama, Japan.
authors.forename: Togo
authors.initials: T
authors.lastname: Ikuta
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kaname
authors.initials: K
authors.lastname: Kawajiri
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D011493:Protein Kinase C