ITAM-coupled NK-cell receptors activate NF-κB, JNK, and p38 via Bcl10 and Malt1. IL-15–expanded NK cells were stimulated with plate-bound anti-NK1.1 and anti-Ly49D antibodies or PMA/Iono for 20 and 60 minutes. Degradation of IκB-α (A) and phosphorylation of ERK, JNK, and p38 (B) was monitored by Western blot. (C) Activation of NF-κB was quantified with a NF-κB p65 transcription factor assay kit using nuclear protein lysates. (D) IFN-γ mRNA levels were quantified by real-time PCR after 24 hours of stimulation as indicated. (E,F) NK cells were stimulated as in Figure 2B,C with anti-NK1.1 and IL-18 either alone or in combination. Cytokine release was measured by ELISA. Data are means plus or minus SD of triplicate samples (where applicable) and representative of 3 independent experiments.