The zebrafish activating immune receptor Nitr9 signals via Dap12

Immunogenetics. 2007 Oct;59(10):813-21. doi: 10.1007/s00251-007-0250-6. Epub 2007 Sep 21.


Both inhibitory and activating forms of natural killer (NK) cell receptors are found in mammals. The activating receptors play a direct role in the recognition of virally infected or transformed cells and transduce activating signals into the cell by partnering with an adaptor protein, which contains a cytoplasmic activation motif. Activating NK receptors encoded by the mammalian leukocyte receptor complex (e.g., killer cell immunoglobulin-like receptors) and the natural killer complex (e.g., Ly49s) partner with the adaptor protein DAP12, whereas NK receptors encoded in the CD94/NKG2 complex partner with the adaptor protein DAP10. Novel immune-type receptors (NITRs) found in bony fish share several common features with immunoglobulin-type NK receptors. Nitr9 is a putative activating receptor in zebrafish that induces cytotoxicity within the context of human NK cells. One isoform of Nitr9, Nitr9L, is shown here to preferentially partner with a zebrafish ortholog of Dap12. Cross-linking the Nitr9L-Dap12 complex results in activation of the phosphytidylinositol 3-kinase-->AKT-->extracellular signal-regulated kinase pathway suggesting that the DAP12-based activating pathway is conserved between bony fish and mammals.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Humans
  • Molecular Sequence Data
  • Phosphorylation
  • Receptors, KIR / genetics
  • Receptors, KIR / immunology
  • Receptors, KIR / metabolism*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction* / immunology
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / immunology
  • Zebrafish Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Nitr9 protein, zebrafish
  • Receptors, KIR
  • Recombinant Proteins
  • Tyrobp protein, zebrafish
  • Zebrafish Proteins

Associated data

  • GENBANK/EF690658