Immunogenetics

, Volume 59, Issue 10, pp 813–821

The zebrafish activating immune receptor Nitr9 signals via Dap12

  • 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
Original Paper

DOI: 10.1007/s00251-007-0250-6

Cite this article as:
Wei, S., Zhou, J., Chen, X. et al. Immunogenetics (2007) 59: 813. doi:10.1007/s00251-007-0250-6

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.

Keywords

Natural cytotoxicityDAP10ERKAKTDAP12NITR

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sheng Wei
    • 1
  • Jun-min Zhou
    • 1
  • Xinghong Chen
    • 1
  • Radhika N. Shah
    • 2
    • 3
  • Jinhong Liu
    • 1
  • Timothy M. Orcutt
    • 2
  • David Traver
    • 4
  • Julie Y. Djeu
    • 1
  • Gary W. Litman
    • 1
    • 5
    • 6
  • Jeffrey A. Yoder
    • 2
    • 3
  1. 1.Immunology ProgramH. Lee Moffitt Cancer Center and Research InstituteTampaUSA
  2. 2.Department of Molecular Biomedical Sciences and Center for Comparative Medicine and Translational Research, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  3. 3.Immunology Program, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  4. 4.Division of Biological Sciences, Section of Cell and Developmental BiologyUniversity of California, San DiegoLa JollaUSA
  5. 5.Department of Molecular GeneticsAll Children’s HospitalSt. PetersburgUSA
  6. 6.Department of Pediatrics, University of South Florida College of MedicineUniversity of South Florida/All Children’s Hospital Children’s Research InstituteSt. PetersburgUSA