Author(s): Turnbull IR, Colonna M
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Abstract 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.
This article was published in Nat Rev Immunol
and referenced in Journal of Clinical & Cellular Immunology