Nature Immunology4, 565 - 572 (2003)
Published online: 11 May 2003; | doi:10.1038/ni930
NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases
Simona Zompi1, Jessica A Hamerman2, Kouetsu Ogasawara2, Edina Schweighoffer3, Victor L J Tybulewicz3, James P Di Santo1, Lewis L Lanier2
& Francesco Colucci1
1
Department of Immunology, Pasteur Institute, 25−28 rue Dr Roux, 75015 Paris, France.
2
Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, HSE 420, Box 0414, San Francisco, California 94143-0414, USA.
3
Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Correspondence should be addressed to Francesco Colucci cecco@pasteur.fr
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.
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