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The Journal of Immunology, 2004, 173: 2470-2478.
Copyright © 2004 by The American Association of Immunologists

A Structural Basis for the Association of DAP12 with Mouse, but Not Human, NKG2D1

David B. Rosen*, Manabu Araki2,{dagger}, Jessica A. Hamerman*, Taian Chen*, Takashi Yamamura{dagger} and Lewis L. Lanier3,*

* Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143; and {dagger} Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo

Prior studies have revealed that alternative mRNA splicing of the mouse NKG2D gene generates receptors that associate with either the DAP10 or DAP12 transmembrane adapter signaling proteins. We report that NKG2D function is normal in human patients lacking functional DAP12, indicating that DAP10 is sufficient for human NKG2D signal transduction. Further, we show that human NKG2D is incapable of associating with DAP12 and provide evidence that structural differences in the transmembrane of mouse and human NKG2D account for the species-specific difference for this immune receptor.




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