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

• Published in: Journal of leukocyte biology Vol. 65; no. 3; pp. 391 - 396
• Main Authors: Caldenhoven, Eric, Buitenhuis, Miranda, Djk, Thamar B., Raaijmakers, Jan A. M., Lammers, Jan‐Willem J., Koenderman, Leo, Groot, Rolf P.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01-03-1999
• Subjects: Antiviral Agents - pharmacology; Cell Differentiation; Cell Lineage; Cells, Cultured; DNA-Binding Proteins - metabolism; gene transcription; HL-60 Cells; Humans; Interferon-gamma - pharmacology; JAK1; JAK2; Janus Kinase 1; Janus Kinase 2; Neutrophils - cytology; Neutrophils - metabolism; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins; Signal Transduction - drug effects; STAT1α; STAT3 Transcription Factor; Trans-Activators - metabolism
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.65.3.391

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.