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Nat Rev Immunol. 2007 Feb;7(2):155-61. Epub 2007 Jan 15.

Activating and inhibitory functions of DAP12.

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Washington University School of Medicine, Department of Pathology and Immunology, Box 8118, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.


When associated with different receptors, the signalling adaptor DAP12 has been shown to both potentiate and attenuate the activation of leukocytes. But how can a protein with a single signalling motif elicit qualitatively different cellular responses? We describe a model of DAP12 function, whereby the quality of the cellular response (activation or inhibition) is modulated by the avidity of the interaction between the DAP12-associated receptor and its ligand. This model extends from previous studies of inhibitory signalling mediated by other adaptors, such as the Fc-receptor gamma-chain and CD3zeta, and provides a potential mechanism for the conflicting phenotypes observed in studies of DAP12-deficient mice.

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