Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases - PubMed (original) (raw)

doi: 10.1038/ni764. Epub 2002 Feb 11.

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• PMID: 11836527
• DOI: 10.1038/ni764

Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases

Francesco Colucci et al. Nat Immunol. 2002 Mar.

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.

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