A Structural basis for the association of DAP12 with mouse, but not human, NKG2D.
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.
Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94143, USA.
David B
DB
Rosen
Manabu
M
Araki
Jessica A
JA
Hamerman
Taian
T
Chen
Takashi
T
Yamamura
Lewis L
LL
Lanier
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002678:Chimera; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011233:Precipitin Tests; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology*; D013045:Species Specificity; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; C120528:HCST protein, human; C492355:Hcst protein, mouse; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C110546:TYROBP protein, human