NKG2D signaling is coupled to the interleukin 15 receptor signaling pathway

Nat Immunol. 2007 Dec;8(12):1345-52. doi: 10.1038/ni1524. Epub 2007 Oct 21.


The effector functions of natural killer cells are regulated by activating receptors, which recognize stress-inducible ligands expressed on target cells and signal through association with signaling adaptors. Here we developed a mouse model in which a fusion of the signaling adaptor DAP10 and ubiquitin efficiently downregulated expression of the activating receptor NKG2D on the surfaces of natural killer cells. With this system, we identified coupling of the signaling pathways triggered by NKG2D and DAP10 to those initiated by the interleukin 15 receptor. We suggest that this coupling of activating receptors to other receptor systems could function more generally to regulate cell type-specific signaling events in distinct physiological contexts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Killer Cells, Natural / physiology*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Models, Animal
  • Models, Biological
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology*
  • Receptors, Interleukin-15 / metabolism
  • Receptors, Interleukin-15 / physiology*
  • Receptors, Natural Killer Cell
  • Signal Transduction*


  • HCST protein, human
  • Klrk1 protein, mouse
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Interleukin-15
  • Receptors, Natural Killer Cell