Dual function for the adaptor MIST in IFN-γ production by NK and CD4+NKT cells regulated by the Src kinase Fgr

Hiroki Sasanuma, Akiko Tatsuno, Shinya Hidano, Keiko Ohshima, Yumi Matsuzaki, Katsuhiko Hayashi, Clifford A. Lowell, Daisuke Kitamura, Ryo Goitsuka

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10 Citations (Scopus)

Abstract

Natural killer (NK) cells and NKT cells play critical early roles in host defense. Here we show that MIST, an adaptor protein belonging to the SLP-76 family, functions negatively in NK cells but positively in CD4+NKT cells. NK-cell receptor-mediated IFN-γ production was enhanced in NK cells, whereas TCR- or NK-cell receptor-mediated cytokine production was reduced in CD4+NKT cells from MIST-deficient mice. These opposite effects of MIST paralleled the exclusive expression of the Src family kinase, Fgr, in NK cells between the 2 cell populations. We further demonstrated that interaction of MIST with Fgr, mediated by the C-terminal proline-rich region of MIST and the SH3 domain of Fgr, was required for the suppression of NK-cell receptor-induced IFN-γ production. This functional interdependence of signaling molecules demonstrates a new mechanism by which adaptor proteins can act as molecular switches to control diverse responses in different cell populations.

Original languageEnglish
Pages (from-to)3647-3655
Number of pages9
JournalBlood
Volume107
Issue number9
DOIs
Publication statusPublished - May 1 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sasanuma, H., Tatsuno, A., Hidano, S., Ohshima, K., Matsuzaki, Y., Hayashi, K., Lowell, C. A., Kitamura, D., & Goitsuka, R. (2006). Dual function for the adaptor MIST in IFN-γ production by NK and CD4+NKT cells regulated by the Src kinase Fgr. Blood, 107(9), 3647-3655. https://doi.org/10.1182/blood-2005-10-4102