Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells.
The adaptors SAP, EAT-2 and ERT are specific to cells of the immune system and belong to the SAP family. All three are expressed in natural killer (NK) cells. Here we examined the global function of the SAP family using mice lacking SAP, EAT-2 and ERT. These adaptors acted together in a mechanism that was essential for the elimination of hematopoietic but not nonhematopoietic cells by NK cells. This function was mediated by many receptors of the SLAM family on NK cells that were engaged by ligands found solely on hematopoietic cells. In the absence of SAP-related adaptors, SLAM receptors lost their activating function and became inhibitory receptors that repressed other activating receptors, such as NKG2D. Hence, the SAP family is essential for the elimination of unwanted hematopoietic cells by NK cells.
Dong
Zhongjun
Z
Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, Montréal, Québec, Canada.
Cruz-Munoz
Mario-Ernesto
ME
Zhong
Ming-Chao
MC
Chen
Riyan
R
Latour
Sylvain
S
Veillette
André
A
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000950:Antigens, Ly / Q000502:physiology; D000071178:CD48 Antigen; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006413:Hematopoietic System / Q000166:cytology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology; D051381:Rats; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000950:Antigens, Ly; D000071178:CD48 Antigen; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D047908:Intracellular Signaling Peptides and Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors; C527086:Klrk1 protein, mouse; C498972:Ly9 protein, mouse; C499569:Sh2d1a protein, mouse; C491225:Sh2d1b1 protein, mouse; C000604063:Slamf6 protein, mouse