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Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada
NK cells are important for innate resistance to tumors and viruses. Engagement of activating Ly-49 receptors expressed by NK cells leads to rapid NK cell activation resulting in target cell lysis and cytokine production. The ITAM-containing DAP12 adapter protein stably associates with activating Ly-49 receptors, and couples receptor recognition with generation of NK responses. Activating Ly-49s are potent stimulators of murine NK cell functions, yet how they mediate such activities is not well understood. We demonstrate that these receptors trigger LFA-1-dependent tight conjugation between NK cells and target cells. Furthermore, we show that activating Ly-49 receptor engagement leads to rapid DAP12-dependent up-regulation of NK cell LFA-1 adhesiveness to ICAM-1 that is also dependent on tyrosine kinases of the Syk and Src families. These results indicate for the first time that activating Ly-49s control adhesive properties of LFA-1, and by DAP12-dependent inside-out signaling. Ly-49-driven mobilization of LFA-1 adhesive function may represent a fundamental proximal event during NK cell interactions with target cells involving activating Ly-49 receptors, leading to target cell death.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Canadian Institutes of Health Research grants (to D.N.B. and K.P.K.). D.N.B. is an Alberta Heritage Foundation for Medical Research senior scholar and K.P.K. is an Alberta Heritage Foundation for Medical Research scientist. M.S.O. was supported by an Alberta Heritage Foundation for Medical Research studentship.
2 Address correspondence and reprint requests to Dr. Deborah N. Burshtyn, Department of Medical Microbiology and Immunology, 6-59 Heritage Medical Research Center, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; E-mail address: burshtyn{at}ualberta.ca or Dr. Kevin P. Kane, Department of Medical Microbiology and Immunology, 660 Heritage Medical Research Center, University of Alberta, Edmonton, Alberta T6G 2S2, Canada; E-mail address: kevin.kane{at}ualberta.ca
3 Abbreviations used in this paper: SFK, Src family kinase; LAT, linker for activation of T cell.
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