Figure 1.

A simplified overview of NK cell activation by the NKG2D pathway. NKG2D upon binding to its specific ligands, MICA/B or ULBPs, associates with adaptor protein DAP10, which is responsible for transducing intracellular activating signaling. NK cell activation depends on the co-engagement of specific activating receptors, such as NKG2D and 2B4, or NKG2D and DNAM-1. These co-engagements induce activation of SLP-76, resulting in Vav1-dependent activation of ERK. Once activated, ERK activates NF-κB or inhibits GSK-3β. NKG2D or DNAM-1 activates another signaling cascade through PI3K and AKT, resulting in GSK-3β inhibition and NF-κB activation. Activation of NF-κB leads to cytokine production and cytolysis of target cells by granzymes and perforins.