The zebrafish activating immune receptor Nitr9 signals via Dap12 |
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| Authors: | Sheng Wei Jun-min Zhou Xinghong Chen Radhika N Shah Jinhong Liu Timothy M Orcutt David Traver Julie Y Djeu Gary W Litman Jeffrey A Yoder |
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| Institution: | (1) Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Avenue, Tampa, FL 33612, USA;(2) Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA;(3) Immunology Program, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA;(4) Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;(5) Department of Molecular Genetics, All Children’s Hospital, 801 Sixth Street South, St. Petersburg, FL 33701, USA;(6) Department of Pediatrics, University of South Florida College of Medicine, University of South Florida/All Children’s Hospital Children’s Research Institute, 830 First Street South, St. Petersburg, FL 33701, USA |
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| Abstract: | 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.
Sheng Wei and Jun-min Zhou contributed equally to this work. |
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| Keywords: | Natural cytotoxicity DAP10 ERK AKT DAP12 NITR |
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