| First Author | Colucci F | Year | 2002 |
| Journal | Nat Immunol | Volume | 3 |
| Issue | 3 | Pages | 288-94 |
| PubMed ID | 11836527 | Mgi Jnum | J:74994 |
| Mgi Id | MGI:2159529 | Doi | 10.1038/ni764 |
| Citation | Colucci F, et al. (2002) Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases. Nat Immunol 3(3):288-94 |
| abstractText | 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. |
