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Publication : Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production.

First Author  Hidano S Year  2008
Journal  Int Immunol Volume  20
Issue  3 Pages  345-52
PubMed ID  18203684 Mgi Jnum  J:131621
Mgi Id  MGI:3774071 Doi  10.1093/intimm/dxm150
Citation  Hidano S, et al. (2008) Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production. Int Immunol 20(3):345-52
abstractText  Activation of NK cells is triggered by multiple receptors. We demonstrate here that SLP-76 is required for CD16- and NKG2D-mediated NK cell cytotoxicity, while MIST negatively regulates these responses in an SLP-76-dependent manner. Exceptionally, MIST acts as a positive regulator of cytotoxicity against YAC-1 cells, although SLP-76 plays a more key role. SLP-76 acts as a dominant positive regulator for both NKG2D-mediated and YAC-1 cell-triggered IFN-gamma production. Although NKG2D-mediated IFN-gamma production depends on phospholipase C (PLC) gamma 2, YAC-1 cell-triggered IFN-gamma production is PLC gamma 2- and Syk/ZAP-70 independent and nuclear factor-kappa B mediated. SLP-76 is required for this process in the presence of MIST but is dispensable in the absence of MIST. Thus, YAC-1 cell-triggered NKG2D-independent IFN-gamma production appears to be regulated by SLP-76-dependent and -independent pathways, in which the latter is negatively regulated by MIST. Taken together, these results suggest that SLP-76 and MIST distinctly but interactively regulate NK cell cytotoxicity and IFN-gamma production.
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