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- Title
Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases.
- Authors
Colucci, Francesco; Schweighoffer, Edina; Tomasello, Elena; Turner, Martin; Ortaldo, John R.; Vivier, Eric; Tybulewicz, Victor L. J.; Di Santo, James P.
- 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 phosphotidyl 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
CELL-mediated cytotoxicity; PROTEIN kinases; IMMUNOLOGY
- Publication
Nature Immunology, 2002, Vol 3, Issue 3, p288
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni764