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| The EMBO Journal
(1998) 17, 3660–3668, doi:10.1093/emboj/17.13.3660 |
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Stat1 combines signals derived from IFN- and LPS receptors during macrophage activation |
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| Pavel Kovarik, Dagmar Stoiber, Michael Novy and Thomas Decker |
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Vienna Biocenter, Institute of Microbiology and Genetics, Dr Bohr-Gasse 9, A-1030 Vienna, Austria To whom correspondence should be addressed Thomas Decker, decker@gem.univie.ac.at Received 29 January 1998; Revised 17 April 1998; Accepted 30 April 1998. |
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| Abstract |
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| Complete activation of macrophages during immune responses results from stimulation with the activating cytokine interferon- (IFN-) and a second stimulus, usually a microbial product. Bacterial infection of macrophages, or treatment with bacterial lipopolysaccharide (LPS), resulted in rapid Stat1 phosphorylation on Ser727 (S727) independently of concomitant tyrosine phosphorylation. IFN- also caused rapid phosphorylation of S727. In both situations, S727 phosphorylation was reduced by pre-treatment of cells with the serine kinase inhibitor H7. When macrophages were treated sequentially or simultaneously with LPS and IFN-, the pool of molecules phosphorylated on both Tyr701 (Y701) and S727 was strongly increased. Consistently, Stat1-dependent transcription in response to IFN- was significantly enhanced if the cells were pre-treated with bacterial LPS. The relative amount of S727-phosphorylated Stat1 in the non-tyrosine phosphorylated fraction was considerably smaller than that in the tyrosine-phosphorylated fraction. No evidence was found for an effect of S727 phosphorylation on the phosphorylation of Y701 by IFN-. Thus, serine and tyrosine phosphorylation of Stat1 are caused independently of each other, but the serine kinase may recognize tyrosine-phosphorylated Stat1 preferentially in the course of an IFN- response. The data suggest Stat1 to be a convergence point for immunological stimuli in a macrophage proinflammatory response. |
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| Keywords: IFN, LPS, serine phosphorylation, Stat, transcription |
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