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

Abstract Binding of interferon-γ (IFN-γ) to its heterodimeric receptor induces activation of the tyrosine kinases JAK1 and JAK2 followed by tyrosine phosphorylation of STAT1α. Selective activation of STAT1α at the IFN-γ receptor is achieved by specific interaction between a cytosolic tyrosine motif including Y440 in the IFN-γ receptor α-chain and the SH2 domain of STAT1α. We demonstrate that, in addition to STAT1α, STAT3 is also activated by IFN-γ 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-γ 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. J. Leukoc. Biol. 65: 391–396; 1999.