Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways
The interferon‐inducible double‐stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)‐2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. He...
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| Veröffentlicht in: | The EMBO Journal 1997-03, Vol.16 (6), p.1291-1304 |
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| creator | Wong, Andrew Hoi-Tao Tam, Nancy Wai Ning Yang, Yi-Li Cuddihy, Andrew R. Li, Suiyang Kirchhoff, Sabine Hauser, Hansjörg Decker, Thomas Koromilas, Antonis E. |
| description | The interferon‐inducible double‐stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)‐2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. Here we report that PKR is involved in IFN‐ and dsRNA‐signaling pathways by modulating the function of the signal transducer and activator of transcription STAT1. We also show that PKR associates with STAT1 in mouse and human cells. The association is not a kinase–substrate interaction since STAT1 phosphorylation is not modified by PKR
in vitro
or
in vivo
. In addition, the formation of the PKR–STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA‐binding domain of PKR. Moreover, there is a concomitant decrease in PKR–STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA‐signaling pathways by modulating the transcriptional function of STAT1. |
| doi_str_mv | 10.1093/emboj/16.6.1291 |
| format | Article |
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in vitro
or
in vivo
. In addition, the formation of the PKR–STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA‐binding domain of PKR. Moreover, there is a concomitant decrease in PKR–STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA‐signaling pathways by modulating the transcriptional function of STAT1.</description><identifier>ISSN: 0261-4189</identifier><identifier>ISSN: 1460-2075</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/16.6.1291</identifier><identifier>PMID: 9135145</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>3T3 Cells ; Animals ; Base Sequence ; DNA - genetics ; DNA - metabolism ; DNA binding ; DNA-Binding Proteins - metabolism ; double-stranded RNA ; eIF-2 Kinase ; HeLa Cells ; Humans ; interferon ; Interferons - metabolism ; Mice ; Mutation ; Phosphorylation ; Protein Binding ; protein phosphorylation ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; RNA, Double-Stranded - metabolism ; Signal Transduction ; STAT1 Transcription Factor ; Trans-Activators - metabolism ; Transcriptional Activation ; Transfection</subject><ispartof>The EMBO Journal, 1997-03, Vol.16 (6), p.1291-1304</ispartof><rights>European Molecular Biology Organization 1997</rights><rights>Copyright © 1997 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6350-b767493de012819d278987ff394a3ace82032a22c605220d78c2cbbf3a5c220e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169727/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169727/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9135145$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Andrew Hoi-Tao</creatorcontrib><creatorcontrib>Tam, Nancy Wai Ning</creatorcontrib><creatorcontrib>Yang, Yi-Li</creatorcontrib><creatorcontrib>Cuddihy, Andrew R.</creatorcontrib><creatorcontrib>Li, Suiyang</creatorcontrib><creatorcontrib>Kirchhoff, Sabine</creatorcontrib><creatorcontrib>Hauser, Hansjörg</creatorcontrib><creatorcontrib>Decker, Thomas</creatorcontrib><creatorcontrib>Koromilas, Antonis E.</creatorcontrib><title>Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways</title><title>The EMBO Journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>The interferon‐inducible double‐stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)‐2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. Here we report that PKR is involved in IFN‐ and dsRNA‐signaling pathways by modulating the function of the signal transducer and activator of transcription STAT1. We also show that PKR associates with STAT1 in mouse and human cells. The association is not a kinase–substrate interaction since STAT1 phosphorylation is not modified by PKR
in vitro
or
in vivo
. In addition, the formation of the PKR–STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA‐binding domain of PKR. Moreover, there is a concomitant decrease in PKR–STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA‐signaling pathways by modulating the transcriptional function of STAT1.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>DNA binding</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>double-stranded RNA</subject><subject>eIF-2 Kinase</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>interferon</subject><subject>Interferons - metabolism</subject><subject>Mice</subject><subject>Mutation</subject><subject>Phosphorylation</subject><subject>Protein Binding</subject><subject>protein phosphorylation</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>RNA, Double-Stranded - metabolism</subject><subject>Signal Transduction</subject><subject>STAT1 Transcription Factor</subject><subject>Trans-Activators - metabolism</subject><subject>Transcriptional Activation</subject><subject>Transfection</subject><issn>0261-4189</issn><issn>1460-2075</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9v0zAcxSMEGmNw5oTkE7e0thPbyQWprGNQxphGgaPlON-03lK7sxNK_xj-V9wfKuPUk2W99z5-yUuS1wQPCC6zISwqdzckfMAHhJbkSXJKco5TigV7mpxiykmak6J8nrwI4Q5jzApBTpKTkmSM5Ow0-XMzXwejVYtUCE4b1RlnUQXdCsCib9PRlCBla9TNARnbgW_AO5saW_faVC2gpXcdGIvujVUB0M3n263fLJZtxG5oATXOPwpv9dr1MZ2Gzscb1Oj2eoSCmVnVGjtDS9XNV2odXibPGtUGeLU_z5LvHy6m5x_Tq6-Xn85HV6nmGcNpJbjIy6wGTGhBypqKoixE02RlrjKloaA4o4pSzTGjFNei0FRXVZMppuMdsrPk3Y677KsF1Bps7NXKpTcL5dfSKSP_V6yZy5n7JQnhpaAiAt7uAd499BA6uTBBQ9sqC64PMhbiOef5USNhJWU5xtE43Bm1dyF4aA5tCJab6eV2ekm45HIzfUy8efwRB_9-66gXO31lWlgfw8mLL-8ngpXxl27K4F00xJSdgZd3rvdxrHC8jVVd7-Hw3D9kutNN6OD3QVb-XnKRCSZ_Xl_K8Rj_GE_YRIrsL-ck6NA</recordid><startdate>19970315</startdate><enddate>19970315</enddate><creator>Wong, Andrew Hoi-Tao</creator><creator>Tam, Nancy Wai Ning</creator><creator>Yang, Yi-Li</creator><creator>Cuddihy, Andrew R.</creator><creator>Li, Suiyang</creator><creator>Kirchhoff, Sabine</creator><creator>Hauser, Hansjörg</creator><creator>Decker, Thomas</creator><creator>Koromilas, Antonis E.</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><scope>BSCLL</scope><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>7TM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19970315</creationdate><title>Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways</title><author>Wong, Andrew Hoi-Tao ; Tam, Nancy Wai Ning ; Yang, Yi-Li ; Cuddihy, Andrew R. ; Li, Suiyang ; Kirchhoff, Sabine ; Hauser, Hansjörg ; Decker, Thomas ; Koromilas, Antonis E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6350-b767493de012819d278987ff394a3ace82032a22c605220d78c2cbbf3a5c220e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>3T3 Cells</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>DNA binding</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>double-stranded RNA</topic><topic>eIF-2 Kinase</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>interferon</topic><topic>Interferons - metabolism</topic><topic>Mice</topic><topic>Mutation</topic><topic>Phosphorylation</topic><topic>Protein Binding</topic><topic>protein phosphorylation</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>RNA, Double-Stranded - metabolism</topic><topic>Signal Transduction</topic><topic>STAT1 Transcription Factor</topic><topic>Trans-Activators - metabolism</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Andrew Hoi-Tao</creatorcontrib><creatorcontrib>Tam, Nancy Wai Ning</creatorcontrib><creatorcontrib>Yang, Yi-Li</creatorcontrib><creatorcontrib>Cuddihy, Andrew R.</creatorcontrib><creatorcontrib>Li, Suiyang</creatorcontrib><creatorcontrib>Kirchhoff, Sabine</creatorcontrib><creatorcontrib>Hauser, Hansjörg</creatorcontrib><creatorcontrib>Decker, Thomas</creatorcontrib><creatorcontrib>Koromilas, Antonis E.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Andrew Hoi-Tao</au><au>Tam, Nancy Wai Ning</au><au>Yang, Yi-Li</au><au>Cuddihy, Andrew R.</au><au>Li, Suiyang</au><au>Kirchhoff, Sabine</au><au>Hauser, Hansjörg</au><au>Decker, Thomas</au><au>Koromilas, Antonis E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways</atitle><jtitle>The EMBO Journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>1997-03-15</date><risdate>1997</risdate><volume>16</volume><issue>6</issue><spage>1291</spage><epage>1304</epage><pages>1291-1304</pages><issn>0261-4189</issn><issn>1460-2075</issn><eissn>1460-2075</eissn><abstract>The interferon‐inducible double‐stranded RNA protein kinase PKR controls protein synthesis through the phosphorylation of eukaryotic translation initiation factor (eIF)‐2. In addition to its demonstrated role in translational control, several reports have suggested a transcriptional role for PKR. Here we report that PKR is involved in IFN‐ and dsRNA‐signaling pathways by modulating the function of the signal transducer and activator of transcription STAT1. We also show that PKR associates with STAT1 in mouse and human cells. The association is not a kinase–substrate interaction since STAT1 phosphorylation is not modified by PKR
in vitro
or
in vivo
. In addition, the formation of the PKR–STAT1 complex is not dependent upon the enzymatic activity of PKR but does require the dsRNA‐binding domain of PKR. Moreover, there is a concomitant decrease in PKR–STAT1 interaction and increase in STAT1 DNA binding in response to IFNs or dsRNA. These findings suggest that PKR plays an important role in IFN and dsRNA‐signaling pathways by modulating the transcriptional function of STAT1.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>9135145</pmid><doi>10.1093/emboj/16.6.1291</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0261-4189 1460-2075 1460-2075 |
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| source | MEDLINE; Wiley Journals; Wiley Free Content; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 3T3 Cells Animals Base Sequence DNA - genetics DNA - metabolism DNA binding DNA-Binding Proteins - metabolism double-stranded RNA eIF-2 Kinase HeLa Cells Humans interferon Interferons - metabolism Mice Mutation Phosphorylation Protein Binding protein phosphorylation Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism RNA, Double-Stranded - metabolism Signal Transduction STAT1 Transcription Factor Trans-Activators - metabolism Transcriptional Activation Transfection |
| title | Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways |
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