Nature Immunology
6, 1002 - 1010 (2005)
Published online: 28 August 2005; Corrected online: 02 September 2005 | doi:10.1038/ni1242
Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptorRomain Roncagalli1, 2, James E R Taylor1, Shaohua Zhang1, Xiaochu Shi1, Riyan Chen1, Mario-Ernesto Cruz-Munoz1, Luo Yin3, Sylvain Latour4
& André Veillette1, 5, 61
Clinical Research Institute of Montréal, Montréal, Québec H2W 1R7, Canada. 2
Program in Molecular Biology, University of Montréal, Montréal, Québec H2W 1R7, Canada. 3
International Agency for Research on Cancer, Lyon 69372, France. 4
Unité INSERM U429, Hôpital Necker Enfants-Malades, Paris 75015, France. 5
Department of Medicine, University of Montréal, Montréal, Québec H3C 3J7, Canada. 6
Department of Medicine, McGill University, Montréal, Québec H3G 1Y6, Canada.
Correspondence should be addressed to André Veillette veillea@ircm.qc.ca 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- 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.* NOTE: In the version of this article initially published online, the sixth line of the abstract was incorrect; it should begin "...its C terminus."
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
