Stat1 combines signals derived from IFN-gamma and LPS receptors during macrophage activation

P Kovarik, D Stoiber, M Novy, T Decker

Research output: Journal article (peer-reviewed)Journal article

204 Citations (Scopus)


Complete activation of macrophages during immune responses results from stimulation with the activating cytokine interferon-gamma (IFN-gamma) 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-gamma 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-gamma, the pool of molecules phosphorylated on both Tyr701 (Y701) and S727 was strongly increased. Consistently, Stat1-dependent transcription in response to IFN-gamma 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-gamma. 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-gamma response. The data suggest Stat1 to be a convergence point for immunological stimuli in a macrophage proinflammatory response.

Original languageEnglish
Pages (from-to)3660-8
Number of pages9
JournalEMBO Journal
Issue number13
Publication statusPublished - 01 Jul 1998
Externally publishedYes


  • Animals
  • Antibodies/immunology
  • Antibody Specificity/immunology
  • Cell Line
  • DNA-Binding Proteins/genetics
  • Enzyme Activation
  • Humans
  • Interferon-gamma/metabolism
  • Lipopolysaccharide Receptors/metabolism
  • Lipopolysaccharides/metabolism
  • Macrophages/drug effects
  • Mice
  • Mitogens/pharmacology
  • Phosphorylation
  • Rabbits
  • Receptors, Interferon/metabolism
  • STAT1 Transcription Factor
  • Salmonella typhimurium/physiology
  • Serine/metabolism
  • Signal Transduction
  • Trans-Activators/genetics
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Tyrosine/metabolism
  • Interferon gamma Receptor


Dive into the research topics of 'Stat1 combines signals derived from IFN-gamma and LPS receptors during macrophage activation'. Together they form a unique fingerprint.

Cite this