Activating and inhibitory functions of DAP12.
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.
Turnbull
Isaiah R
IR
Washington University School of Medicine, Department of Pathology and Immunology, Box 8118, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.
Colonna
Marco
M
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D015398:Signal Transduction / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C484963:Tyrobp protein, mouse