Signal transduction during NK cell activation: balancing opposing forces.

Significant progress has been made in our understanding of the basic signaling mechanisms regulating NK cell activation. Advances have been fueled in part by the molecular characterization of specific activating receptors (e.g., the Fc gamma RIII multi-subunit complex) and inhibitory receptors (e.g., novel MHC-recognizing inhibitory receptors). However, certain aspects of these analyses are complicated by the heterogeneous nature of the receptor-ligand interactions utilized during the development of a cytotoxic response. Future advances will depend in part on the further molecular characterization of the involved receptors and second messengers and on the development of experimental models for genetically manipulating the signaling elements. It will remain important to understand both activating and inhibitory signaling pathways as the emerging theme is that the balance of these two opposing forces determines the functional outcome of an NK cells interaction with its target.