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Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor.

EAT-2 is an adaptor expressed in innate immune cells, including natural killer (NK) cells. It is closely related to the adaptor SAP, which regulates signaling lymphocyte activation molecule (SLAM)-related receptors by recruiting the kinase FynT to the receptors. Here we have studied the function of EAT-2 in NK cells by creating mice lacking or overexpressing EAT-2. Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells. However, unlike SAP, EAT-2 was an inhibitor of NK cell function. EAT-2 repressed natural cytotoxicity and interferon-gamma secretion by a mechanism involving tyrosine phosphorylation of its C terminus. We have demonstrated a similar function for the adaptor ERT, a newly identified SAP family member expressed in mouse NK cells. These data identify a previously unknown mechanism of NK cell inhibition. Moreover, they indicate that EAT-2 and SAP have distinct and at times opposing functions in natural immunity.

Pubmed ID: 16127454

Authors

  • Roncagalli R
  • Taylor JE
  • Zhang S
  • Shi X
  • Chen R
  • Cruz-Munoz ME
  • Yin L
  • Latour S
  • Veillette A

Journal

Nature immunology

Publication Data

October 22, 2005

Associated Grants

None

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Antigens, CD
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cytotoxicity, Immunologic
  • Down-Regulation
  • Interferon-gamma
  • Intracellular Signaling Peptides and Proteins
  • Killer Cells, Natural
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Molecular Sequence Data
  • Phosphorylation
  • Receptors, Immunologic
  • Sequence Alignment
  • Transcription Factors
  • Tyrosine
  • src Homology Domains