Redundant role of the Syk protein tyrosine kinase in mouse NK cell differentiation.
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.
Colucci
F
F
Babraham Institute, Cambridge, UK.
Turner
M
M
Schweighoffer
E
E
Guy-Grand
D
D
Di Bartolo
V
V
Salcedo
M
M
Tybulewicz
V L
VL
Di Santo
J P
JP
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D000941:Antigens / Q000502:physiology; D015703:Antigens, CD; D000950:Antigens, Ly; D000954:Antigens, Surface; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002678:Chimera / Q000276:immunology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics; D004792:Enzyme Precursors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005333:Fetus; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D054340:Receptors, KIR; D015398:Signal Transduction / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D000072377:Syk Kinase
D000941:Antigens; D015703:Antigens, CD; D000950:Antigens, Ly; D000954:Antigens, Surface; C490007:Cd244a protein, mouse; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D000071176:Signaling Lymphocytic Activation Molecule Family; C064655:V(D)J recombination activating protein 2; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse