Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor
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, A...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2004-04, Vol.317 (2), p.545-550 |
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| creator | Ikuta, Togo Kobayashi, Yasuhito Kawajiri, Kaname |
| description | 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. |
| doi_str_mv | 10.1016/j.bbrc.2004.03.076 |
| format | Article |
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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. 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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.</description><subject>Active Transport, Cell Nucleus - physiology</subject><subject>AhR</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>Cell Nucleus - metabolism</subject><subject>Dogs</subject><subject>Humans</subject><subject>Immunostaining</subject><subject>In vitro nuclear transport</subject><subject>Ligands</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microinjection</subject><subject>NLS</subject><subject>Nuclear import</subject><subject>Phosphorylation</subject><subject>PKC</subject><subject>Protein Binding</subject><subject>Protein Kinase C - chemistry</subject><subject>Protein Kinase C - metabolism</subject><subject>Receptors, Aryl Hydrocarbon - chemistry</subject><subject>Receptors, Aryl Hydrocarbon - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Structure-Activity Relationship</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1r3DAQhkVpaTZJ_0APxafe7IzkD9mQSwlpGwi0hxZyE_oYx1q0kitpS9JfXy27pLeeBob3fZh5CHlPoaFAh6tto1TUDQPoGmgb4MMrsqEwQc0odK_JBgCGmk304Yycp7QFoLQbprfkjPYwtHxiG_L0fQlpXUJ8djLb4KswV36vHcpYuaCls3-O-2QfvXSV9YtVNqcqL1g5-yi9qQ2u6A36_NK0uzXEfGDJAq6WZxMLK6rCiahxzSFekjezdAnfneYF-fn59sfN1_r-25e7m0_3te7omGszS9UrBmzuqZSm40yPYJTSAwWmpez0qAFb6Me544NUE0fOuR7mburbibP2gnw8ctcYfu0xZbGzSaNz0mPYJ8HpCG3fjiXIjkEdQ0oRZ7FGuyv3Cwri4FtsxcG3OPgW0Iriu5Q-nOh7tUPzr3ISXALXxwCWH39bjCJpi16jscVEFibY__H_AmLLlOM</recordid><startdate>20040430</startdate><enddate>20040430</enddate><creator>Ikuta, Togo</creator><creator>Kobayashi, Yasuhito</creator><creator>Kawajiri, Kaname</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040430</creationdate><title>Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor</title><author>Ikuta, Togo ; Kobayashi, Yasuhito ; Kawajiri, Kaname</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-dfab5b202f51aad472c80dbbc6102caa4c8c0e3058f476ab97e777c6f49539723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Active Transport, Cell Nucleus - physiology</topic><topic>AhR</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Cell Line</topic><topic>Cell Nucleus - metabolism</topic><topic>Dogs</topic><topic>Humans</topic><topic>Immunostaining</topic><topic>In vitro nuclear transport</topic><topic>Ligands</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microinjection</topic><topic>NLS</topic><topic>Nuclear import</topic><topic>Phosphorylation</topic><topic>PKC</topic><topic>Protein Binding</topic><topic>Protein Kinase C - chemistry</topic><topic>Protein Kinase C - metabolism</topic><topic>Receptors, Aryl Hydrocarbon - chemistry</topic><topic>Receptors, Aryl Hydrocarbon - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ikuta, Togo</creatorcontrib><creatorcontrib>Kobayashi, Yasuhito</creatorcontrib><creatorcontrib>Kawajiri, Kaname</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ikuta, Togo</au><au>Kobayashi, Yasuhito</au><au>Kawajiri, Kaname</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2004-04-30</date><risdate>2004</risdate><volume>317</volume><issue>2</issue><spage>545</spage><epage>550</epage><pages>545-550</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15063792</pmid><doi>10.1016/j.bbrc.2004.03.076</doi><tpages>6</tpages></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 2004-04, Vol.317 (2), p.545-550 |
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| subjects | Active Transport, Cell Nucleus - physiology AhR Animals Binding Sites Cell Line Cell Nucleus - metabolism Dogs Humans Immunostaining In vitro nuclear transport Ligands Liver - metabolism Male Mice Mice, Inbred C57BL Microinjection NLS Nuclear import Phosphorylation PKC Protein Binding Protein Kinase C - chemistry Protein Kinase C - metabolism Receptors, Aryl Hydrocarbon - chemistry Receptors, Aryl Hydrocarbon - metabolism Signal Transduction - physiology Structure-Activity Relationship |
| title | Phosphorylation of nuclear localization signal inhibits the ligand-dependent nuclear import of aryl hydrocarbon receptor |
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