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© Research
Publication : Nature immunology

NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature immunology - 11 May 2003

Zompi S, Hamerman JA, Ogasawara K, Schweighoffer E, Tybulewicz VL, Di Santo JP, Lanier LL, Colucci F

Link to Pubmed [PMID] – 12740576

Nat. Immunol. 2003 Jun;4(6):565-72

In activated mouse natural killer (NK) cells, the NKG2D receptor associates with two intracellular adaptors, DAP10 and DAP12, which trigger phosphatidyl inositol 3 kinase (PI3K) and Syk family protein tyrosine kinases, respectively. Here we show that cytotoxicity, but not cytokine production, is triggered by NKG2D in activated NK cells lacking either DAP12 or the Syk family members Syk and ZAP70. Inhibition of PI3K blocks this cytotoxicity, suggesting that the DAP10-PI3K pathway is sufficient to initiate NKG2D-mediated killing of target cells. Our results highlight signaling divergence in the effector functions of NKG2D and indicate that alternative associations between a receptor and its adaptors may provide a single receptor with a dual ‘on-switch’, giving mouse NK cells more choices through which to trigger cytotoxicity.

http://www.ncbi.nlm.nih.gov/pubmed/12740576