1. Activation of a Functionally Distinct 80-kDa STAT5 Isoform by IL-5 and GM-CSF in Human Eosinophils and Neutrophils
- Author
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Eric Caldenhoven, Thamar B. van Dijk, Jan A. M. Raaijmakers, Leo Koenderman, Jan-Willem J. Lammers, and Rolf P. de Groot
- Subjects
Cell Extracts ,Gene isoform ,Neutrophils ,HL-60 Cells ,Plasma protein binding ,STAT5 Transcription Factor ,Humans ,Protein Isoforms ,Phosphorylation ,Receptor ,Molecular Biology ,Interleukin 5 ,STAT5 ,biology ,Tumor Suppressor Proteins ,Granulocyte-Macrophage Colony-Stimulating Factor ,food and beverages ,JAK-STAT signaling pathway ,Milk Proteins ,Molecular biology ,DNA-Binding Proteins ,Eosinophils ,Molecular Weight ,Haematopoiesis ,Trans-Activators ,biology.protein ,Interleukin-5 ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
Interleukin-5 (IL-5), IL-3, and granulocyte macrophage colony-stimulating factor (GM-CSF) are hematopoietic cytokines which signal through a common beta subunit (betac) of a heterodimeric receptor. Among the intracellular signaling pathways activated via betac is the JAK/STAT pathway. We show that different STAT5 isoforms are activated by IL-5 and GM-CSF in eosinophils, neutrophils, and differentiated eosinophilic HL-60 cells. Whereas IL-5 activated the wild-type STAT5A and STAT5B proteins in HL60-eos cells, a carboxyl-terminally truncated 80-kDa STAT5 isoform was activated in mature eosinophils and neutrophils. Surprisingly, while both isoforms bind strongly to an element from the beta-casein promoter, only p80 STAT5 binds to the ICAM1-IRE. Consequently, a carboxyl-terminal truncated STAT5 is capable of blocking STAT3-mediated transcription of an IREtkCAT reporter construct. The cell type-specific expression of these functionally distinct STAT5 isoforms might contribute to the pleiotropic effects of IL-5 and GM-CSF on different target cells.
- Published
- 1999