Lineage-specific activation of STAT3 by interferon-gamma in human neutrophils

J Leukoc Biol. 1999 Mar;65(3):391-6. doi: 10.1002/jlb.65.3.391.


Binding of interferon-gamma (IFN-gamma) to its heterodimeric receptor induces activation of the tyrosine kinases JAK1 and JAK2 followed by tyrosine phosphorylation of STAT1alpha. Selective activation of STAT1alpha at the IFN-gamma receptor is achieved by specific interaction between a cytosolic tyrosine motif including Y440 in the IFN-gamma receptor alpha-chain and the SH2 domain of STAT1alpha. We demonstrate that, in addition to STAT1alpha, STAT3 is also activated by IFN-gamma in human neutrophils. The activation of STAT3 was not found in human eosinophils, monocytes, and HL-60 cells, although the STAT3 protein was expressed in these cells. The cell type-specific activation of STAT3 by IFN-gamma was also observed in neutrophils that are differentiated in vitro from human CD34+ hematopoietic stem cells. These results indicate that a single cytokine receptor can activate different STAT family members in a cell-specific manner, which might result in cell-specific gene transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • HL-60 Cells
  • Humans
  • Interferon-gamma / pharmacology*
  • Janus Kinase 1
  • Janus Kinase 2
  • Neutrophils / cytology*
  • Neutrophils / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins*
  • STAT3 Transcription Factor
  • Signal Transduction / drug effects
  • Trans-Activators / metabolism*


  • Antiviral Agents
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2