ZFIN ID: ZDB-PUB-071001-7
The zebrafish activating immune receptor Nitr9 signals via Dap12
Wei, S., Zhou, J.M., Chen, X., Shah, R.N., Liu, J., Orcutt, T.M., Traver, D., Djeu, J.Y., Litman, G.W., and Yoder, J.A.
Date: 2007
Source: Immunogenetics   59(10): 813-821 (Journal)
Registered Authors: Litman, Gary W., Orcutt, Timothy, Shah, Radhika, Traver, David, Yoder, Jeffrey A.
Keywords: Natural cytotoxicity, DAP10, ERK, AKT, DAP12, NITR
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*
PubMed: 17891481 Full text @ Immunogenetics
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.