Interaction of STAT5 Dimers on Two Low Affinity Binding Sites Mediates Interleukin 2 (IL-2) Stimulation of IL-2 Receptor α Gene Transcription
Stimulation of the interleukin 2 receptor α (IL-2Rα) gene by IL-2 is important for the proliferation of antigen-activated T lymphocytes. IL-2 regulates IL-2Rα transcription via a conserved 51-nucleotide IL-2 responsive enhancer. Mouse enhancer function depends on cooperative activity of three distin...
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| Veröffentlicht in: | The Journal of biological chemistry 1997-12, Vol.272 (50), p.31821-31828 |
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| container_end_page | 31828 |
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| container_issue | 50 |
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| container_title | The Journal of biological chemistry |
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| creator | Meyer, Wolfram K.-H. Reichenbach, Patrick Schindler, Ulrike Soldaini, Elisabetta Nabholz, Markus |
| description | Stimulation of the interleukin 2 receptor α (IL-2Rα) gene by IL-2 is important for the proliferation of antigen-activated T lymphocytes. IL-2 regulates IL-2Rα transcription via a conserved 51-nucleotide IL-2 responsive enhancer. Mouse enhancer function depends on cooperative activity of three distinct sites. Two of these are weak binding sites for IL-2-activated STAT5 (signal transducer and activator of transcription) proteins, and mutational analysis indicates that binding of STAT5 to both sites is required for IL-2 responsiveness of the enhancer. The STAT5 dimers interact to form a STAT5 tetramer. The efficiency of tetramerization depends on the relative rotational orientation of the two STAT motifs on the DNA helix. STAT5 tetramerization on enhancer mutants correlates well with the IL-2 responsiveness of these mutants. This provides strong evidence that interactions between STAT dimers binding to a pair of weak binding sites play a biological role by controlling the activity of a well characterized, complex cytokine-responsive enhancer. |
| doi_str_mv | 10.1074/jbc.272.50.31821 |
| format | Article |
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IL-2 regulates IL-2Rα transcription via a conserved 51-nucleotide IL-2 responsive enhancer. Mouse enhancer function depends on cooperative activity of three distinct sites. Two of these are weak binding sites for IL-2-activated STAT5 (signal transducer and activator of transcription) proteins, and mutational analysis indicates that binding of STAT5 to both sites is required for IL-2 responsiveness of the enhancer. The STAT5 dimers interact to form a STAT5 tetramer. The efficiency of tetramerization depends on the relative rotational orientation of the two STAT motifs on the DNA helix. STAT5 tetramerization on enhancer mutants correlates well with the IL-2 responsiveness of these mutants. This provides strong evidence that interactions between STAT dimers binding to a pair of weak binding sites play a biological role by controlling the activity of a well characterized, complex cytokine-responsive enhancer.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.272.50.31821</identifier><identifier>PMID: 9395528</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Base Sequence ; Binding Sites ; Cell Line ; Dimerization ; DNA - metabolism ; DNA-Binding Proteins - metabolism ; Interleukin-2 - pharmacology ; Mice ; Milk Proteins ; Molecular Sequence Data ; Protein Binding ; Receptors, Interleukin-2 - genetics ; STAT5 Transcription Factor ; Trans-Activators - metabolism ; Transcription, Genetic</subject><ispartof>The Journal of biological chemistry, 1997-12, Vol.272 (50), p.31821-31828</ispartof><rights>1997 © 1997 ASBMB. 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This provides strong evidence that interactions between STAT dimers binding to a pair of weak binding sites play a biological role by controlling the activity of a well characterized, complex cytokine-responsive enhancer.</description><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>Dimerization</subject><subject>DNA - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Interleukin-2 - pharmacology</subject><subject>Mice</subject><subject>Milk Proteins</subject><subject>Molecular Sequence Data</subject><subject>Protein Binding</subject><subject>Receptors, Interleukin-2 - genetics</subject><subject>STAT5 Transcription Factor</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription, Genetic</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi1EVZbCnQuSTwgOWWzHTmxuS6FlpUVIbJC4WY4zRi6Js9gJVV-Cd-FF-kx4u0tviLnM6J9_vsP8CD2jZElJzV9ftXbJarYUZFlSyegDtKBElkUp6NeHaEEIo4ViQj5Cj1O6Irm4oqfoVJVKCCYX6Nc6TBCNnfwY8Ojwtlk1Ar_zA8SEs9Rcj3gzXuOVcz746Qa_9aHz4Rve-gkS_gidN_vhDtPD_N0HzPDL9aZgr_B28sPcm7_svYg_g4XdNEZ8-xtfQgDcRBOSjX63tz1BJ870CZ4e-xn6cvG-Of9QbD5drs9Xm8JyKqeiaqUyUolW1a2UtVOctrKSQjhlXVlabgkz0lgqBWNtV5dWuYq5VmSBM8bLM_TiwN3F8ccMadKDTxb63gQY56RrxSsuKPmvkVYlqSqqspEcjDaOKUVwehf9YOKNpkTvs9I5K52z0oLou6zyyfMje24H6O4PjuHk_ZvDHvInfnqIOlkPweafR7CT7kb_b_gfziqiTw</recordid><startdate>19971212</startdate><enddate>19971212</enddate><creator>Meyer, Wolfram K.-H.</creator><creator>Reichenbach, Patrick</creator><creator>Schindler, Ulrike</creator><creator>Soldaini, Elisabetta</creator><creator>Nabholz, Markus</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>19971212</creationdate><title>Interaction of STAT5 Dimers on Two Low Affinity Binding Sites Mediates Interleukin 2 (IL-2) Stimulation of IL-2 Receptor α Gene Transcription</title><author>Meyer, Wolfram K.-H. ; Reichenbach, Patrick ; Schindler, Ulrike ; Soldaini, Elisabetta ; Nabholz, Markus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-6b89a895b97b887f941b86855f9cf33c4c02a8ac18522bd73c9f62fb518542243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Cell Line</topic><topic>Dimerization</topic><topic>DNA - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Interleukin-2 - pharmacology</topic><topic>Mice</topic><topic>Milk Proteins</topic><topic>Molecular Sequence Data</topic><topic>Protein Binding</topic><topic>Receptors, Interleukin-2 - genetics</topic><topic>STAT5 Transcription Factor</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meyer, Wolfram K.-H.</creatorcontrib><creatorcontrib>Reichenbach, Patrick</creatorcontrib><creatorcontrib>Schindler, Ulrike</creatorcontrib><creatorcontrib>Soldaini, Elisabetta</creatorcontrib><creatorcontrib>Nabholz, Markus</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meyer, Wolfram K.-H.</au><au>Reichenbach, Patrick</au><au>Schindler, Ulrike</au><au>Soldaini, Elisabetta</au><au>Nabholz, Markus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction of STAT5 Dimers on Two Low Affinity Binding Sites Mediates Interleukin 2 (IL-2) Stimulation of IL-2 Receptor α Gene Transcription</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1997-12-12</date><risdate>1997</risdate><volume>272</volume><issue>50</issue><spage>31821</spage><epage>31828</epage><pages>31821-31828</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Stimulation of the interleukin 2 receptor α (IL-2Rα) gene by IL-2 is important for the proliferation of antigen-activated T lymphocytes. 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| ispartof | The Journal of biological chemistry, 1997-12, Vol.272 (50), p.31821-31828 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Base Sequence Binding Sites Cell Line Dimerization DNA - metabolism DNA-Binding Proteins - metabolism Interleukin-2 - pharmacology Mice Milk Proteins Molecular Sequence Data Protein Binding Receptors, Interleukin-2 - genetics STAT5 Transcription Factor Trans-Activators - metabolism Transcription, Genetic |
| title | Interaction of STAT5 Dimers on Two Low Affinity Binding Sites Mediates Interleukin 2 (IL-2) Stimulation of IL-2 Receptor α Gene Transcription |
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