title: Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-gamma production.
abstract: 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.
authors.affiliation: Division of Development and Aging, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba 278-0022, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hidano
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasanuma
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohshima
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Seino
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Hikida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
authors.forename: Ryo
authors.initials: R
authors.lastname: Goitsuka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C488191:Clnk protein, mouse; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins; D007371:Interferon-gamma