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Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases.
- Source :
-
Nature immunology [Nat Immunol] 2002 Mar; Vol. 3 (3), pp. 288-94. Date of Electronic Publication: 2002 Feb 11. - Publication Year :
- 2002
-
Abstract
- The intracellular signals that trigger natural cytotoxicity have not been clearly determined. The Syk and ZAP-70 tyrosine kinases are essential for cellular activation initiated by B and T cell antigen receptors and may drive natural killer (NK) cell cytotoxicity via receptors bearing immunoreceptor tyrosine-based activation motifs (ITAMs). However, we found that, unlike B and T cells, NK cells developed in Syk-/-ZAP-70-/- mice and, despite their nonfunctional ITAMs, lysed various tumor targets in vitro and eliminated tumor cells in vivo, including those without NKG2D ligands. The simultaneous inhibition of phosphatidyl inositol 3 kinase and Src kinases abrogated the cytolytic activity of Syk-/-ZAP-70-/- NK cells and strongly reduced that of wild-type NK cells. This suggests that distinct and redundant signaling pathways act synergistically to trigger natural cytotoxicity.
- Subjects :
- Animals
Intracellular Signaling Peptides and Proteins
Lymphocyte Activation
Mice
Mice, Inbred C57BL
NK Cell Lectin-Like Receptor Subfamily K
Receptors, Immunologic physiology
Receptors, Natural Killer Cell
Syk Kinase
ZAP-70 Protein-Tyrosine Kinase
Cytotoxicity, Immunologic
Enzyme Precursors physiology
Killer Cells, Natural immunology
Protein-Tyrosine Kinases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2908
- Volume :
- 3
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 11836527
- Full Text :
- https://doi.org/10.1038/ni764