The zebrafish activating immune receptor Nitr9 signals via Dap12.
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.
Wei
Sheng
S
Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Avenue, Tampa, FL 33612, USA.
Zhou
Jun-Min
JM
Chen
Xinghong
X
Shah
Radhika N
RN
Liu
Jinhong
J
Orcutt
Timothy M
TM
Traver
David
D
Djeu
Julie Y
JY
Litman
Gary W
GW
Yoder
Jeffrey A
JA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D054340:Receptors, KIR / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C524871:Nitr9 protein, zebrafish; D054340:Receptors, KIR; D011994:Recombinant Proteins; C524872:Tyrobp protein, zebrafish; D029961:Zebrafish Proteins