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 γ-chain and CD3ζ, and provides a potential mechanism for the conflicting phenotypes observed in studies of DAP12-deficient mice.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalNature Reviews Immunology
Issue number2
StatePublished - Feb 2007


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