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| The EMBO Journal
(2001) 20, 91–100, doi: 10.1093/emboj/20.1.91 |
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| Specificity of signaling by STAT1 depends on SH2 and C-terminal domains that regulate Ser727 phosphorylation, differentially affecting specific target gene expression |
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| Pavel Kovarik1, Monika Mangold1, Katrin Ramsauer1, Hamid Heidari1, Ralf Steinborn2, Angelika Zotter1, David E. Levy3, Mathias Müller2 and Thomas Decker1 |
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1 Vienna Biocenter, Institute of Microbiology and Genetics, Dr. Bohr-Gasse 9, A-1030 Vienna, Austria 2 Institute of Animal Breeding and Genetics, Veterinary University of Vienna, Veterinärplatz 1, A-1210 Vienna, Austria 3 Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY 10016, USA To whom correspondence should be addressed Pavel Kovarik, pavel@gem.univie.ac.at Thomas Decker, decker@gem.univie.ac.at Received 28 August 2000; Revised 16 November 2000; Accepted 20 November 2000. |
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| Abstract |
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Complete activation of signal transducer and activator of transcription 1 (STAT1) requires phosphorylation at both Y701 and a conserved PMS727P sequence. S727 phosphorylation of STAT1 in interferon- (IFN-)-treated mouse fibroblasts occurred without a need for p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 or c-Jun kinases, and required both an intact SH2 domain and phosphorylation of Y701. In contrast, UV irradiation-induced STAT1 phosphorylation on S727 required p38MAPK, but no SH2 domain− phosphotyrosine interactions. Mutation of S727 differentially affected IFN- target genes, at the level of both basal and induced expression. Particularly strong effects were noted for the GBP1 and TAP1 genes. The PMS727P motif of STAT3 was phosphorylated by stimuli and signaling pathways different from those for STAT1 S727. Transfer of the STAT3 C-terminus to STAT1 changed the stimulus and pathway specificity of STAT1 S727 phosphorylation to that of STAT3. Our data suggest that STAT C-termini contribute to the specificity of cellular responses by linking individual STATs to different serine kinase pathways and through an intrinsically different requirement for serine phosphorylation at different target gene promoters. |
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| Keywords: phosphorylation, signal transduction, STAT1, transcription |
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