Viewpoint: Signal transduction during natural killer cell activation

The various subsets of lymphocytes all express multisubunit immune recognition receptors. However, this 'viewpoint' forwards the perspective that receptor ligation on natural killer (NK) cells initiates a subset of signaling events that are specifically linked to specialized cytotoxic lymphocyte functions. This includes roles for src-family protein tyrosine kinases and phosphatidylinositol 3-kinase in coupling receptor stimulation to granule release and cell-mediated cytotoxicity. Novel receptors (e.g. receptors recognizing MHC class I, or carbohydrate domains) also clearly generate signals modulating NK cell activation. Emerging data also suggest that alternative modes of NK-cell-mediated killing (i.e. antibody-dependent cellular cytotoxicity vs. natural cytotoxicity) are regulated by distinct signaling pathways. Discussion is provided on the technological approaches that seem most likely to advance our understanding of how receptor-initiated signals in NK cells precisely control their cellular responses.