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Redundant role of the Syk protein tyrosine kinase in mouse NK cell differentiation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1999 Aug 15; Vol. 163 (4), pp. 1769-74. - Publication Year :
- 1999
-
Abstract
- Syk and ZAP-70 subserve nonredundant functions in B and T lymphopoiesis. In the absence of Syk, B cell development is blocked, while T cell development is arrested in the absence of ZAP-70. The receptors and the signaling molecules required for differentiation of NK cells are poorly characterized. Here we investigate the role of the Syk protein tyrosine kinase in NK cell differentiation. Hemopoietic chimeras were generated by reconstituting alymphoid (B-, T-, NK-) recombinase-activating gene-2 x common cytokine receptor gamma-chain double-mutant mice with Syk-/- fetal liver cells. The phenotypically mature Syk-/- NK cells that developed in this context were fully competent in natural cytotoxicity and in calibrating functional inhibitory receptors for MHC molecules. Syk-deficient NK cells demonstrated reduced levels of Ab-dependent cellular cytotoxicity. Nevertheless, Syk-/- NK cells could signal through NK1. 1 and 2B4 activating receptors and expressed ZAP-70 protein. We conclude that the Syk protein tyrosine kinase is not essential for murine NK cell development, and that compensatory signaling pathways (including those mediated through ZAP-70) may sustain most NK cell functions in the absence of Syk.
- Subjects :
- Animals
Antibody-Dependent Cell Cytotoxicity genetics
Antigens physiology
Antigens, Ly
Antigens, Surface
Cell Differentiation genetics
Cell Differentiation immunology
Chimera immunology
Crosses, Genetic
DNA-Binding Proteins genetics
Enzyme Precursors deficiency
Enzyme Precursors genetics
Fetus
Hematopoiesis genetics
Hematopoiesis immunology
Immunity, Cellular genetics
Intracellular Signaling Peptides and Proteins
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Lectins, C-Type
Liver metabolism
Lymphocyte Activation genetics
Membrane Glycoproteins physiology
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily B
Protein-Tyrosine Kinases deficiency
Protein-Tyrosine Kinases genetics
Proteins physiology
Receptors, Immunologic physiology
Receptors, KIR
Signal Transduction immunology
Signaling Lymphocytic Activation Molecule Family
Syk Kinase
Antigens, CD
Enzyme Precursors physiology
Killer Cells, Natural cytology
Killer Cells, Natural enzymology
Protein-Tyrosine Kinases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 163
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 10438908