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

Binding of interferon-gamma (IFN-gamma) to its heterodimeric receptor induc es activation of the tyrosine kinases JAK1 and JAK2 followed by tyrosine ph osphorylation of STAT1 alpha. Selective activation of STAT1 alpha at the IF N-gamma receptor is achieved by specific interaction between a cytosolic ty rosine motif including Y440 in the IFN-gamma receptor alpha-chain and the S H2 domain of STAT1 alpha. We demonstrate that, in addition to STAT1 alpha, STAT3 is also activated by IFN-gamma in human neutrophils. The activation o f STAT3 was not found in human eosinophils, monocytes, and HL-60 cells, alt hough the STAT3 protein was expressed in these cells. The cell type-specifi c activation of STAT3 by IFN-gamma was also observed in neutrophils that ar e differentiated in vitro from human CD34(+) hematopoietic stem cells. Thes e results indicate that a single cytokine receptor can activate different S TAT family members in a cell-specific manner, which might result in cell-sp ecific gene transcription.