Identification of a STAT6 domain required for IL-4-induced activation of transcription.
Tyrosine phosphorylation of STAT6 in response to IL-4 results in the formation of STAT6 homodimers that bind specific DNA elements. Although binding sites for STAT6 have been shown to be important for the function of several IL-4-inducible promoters, the role of STAT6 in this activation has not been defined. To determine whether STAT6 is a transcriptional activator, different portions of the carboxyl terminus of STAT6 were fused to the yeast Gal4 protein DNA binding domain. Analysis of these chimeric Gal4-STAT6 proteins demonstrates that a 140-amino-acid proline-rich region of the carboxyl terminus of STAT6 contains a region that activates transcription. Truncation mutants of STAT6 that lack this domain cannot activate transcription and are capable of repressing transcription stimulated by a wild-type STAT6 protein. Strikingly, the ability of IL-4 to induce transcription from the Ig germline epsilon promoter is suppressed by overexpression of a carboxyl-terminal deletion mutant of STAT6. These studies demonstrate that the carboxyl terminus of STAT6 contains an activating domain required for the induction of genes by IL-4.
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Integrated Program in Molecular, Cellular, and Biophysical Studies, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Reichel
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Fisher
D A
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Smith
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Rothman
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D000595:Amino Acid Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011392:Proline / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000276:immunology; D017434:Protein Structure, Tertiary; D050800:STAT6 Transcription Factor; D017384:Sequence Deletion; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000276:immunology*
D004268:DNA-Binding Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D011392:Proline