Activating and inhibitory functions of DAP12

Nat Rev Immunol. 2007 Feb;7(2):155-61. doi: 10.1038/nri2014. Epub 2007 Jan 15.


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.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Humans
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Signal Transduction / immunology


  • Adaptor Proteins, Signal Transducing
  • Tyrobp protein, mouse