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Axl/Gas6 pathway participates in human natural killer cell development by positively regulating FLT3 activation
- Publication Year :
- 2013
-
Abstract
- Activation of the fibromyalgia syndrome-like tyrosine kinase 3 (FLT3) by its ligand, FLT3 ligand (FL), strongly augments the development of natural killer (NK) cells from human CD34⁺ hematopoietic progenitor cells (HPCs) in the presence of IL-15, compared with NK-cell development in the presence of IL-15 alone. In this study, we observed that blocking the receptor tyrosine kinase Axl/Gas6 pathway with a soluble Axl-IgG1 Fc fusion protein (Axl-Fc) in the presence of FL significantly diminished the absolute number of CD3⁻ CD56⁺ NK cells derived from human CD34⁺ HPCs. Axl-Fc reduced the expression levels of the IL-2/15 receptor β chain (CD122) and γ chain (CD132) induced by activation of FLT3 and consequently reduced the frequency of NK precursor cells responding to IL-15. Furthermore, Axl-Fc diminished FL-induced FLT3 phosphorylation and impeded the physical interaction between Axl and FLT3 in CD34⁺ HPCs. Collectively, our data suggest that the Axl/Gas6 pathway contributes to normal human NK-cell development at least in part via its positive regulatory effect on FLT3 signaling in CD34⁺ HPCs.
- Subjects :
- Interleukin-15
Recombinant Fusion Proteins
Receptor Protein-Tyrosine Kinases
hemic and immune systems
Antigens, CD34
Cell Differentiation
Hematopoietic Stem Cells
Lymphocyte Activation
Axl Receptor Tyrosine Kinase
Article
Immunoglobulin Fc Fragments
Interleukin-2 Receptor beta Subunit
Killer Cells, Natural
fms-Like Tyrosine Kinase 3
Proto-Oncogene Proteins
embryonic structures
Humans
Intercellular Signaling Peptides and Proteins
Phosphorylation
Cells, Cultured
Interleukin Receptor Common gamma Subunit
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.pmid..........2c0900888c57f40e2ae9ab82ee8c1171