Activating Ly-49 receptors regulate LFA-1-mediated adhesion by NK cells.
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.
Osman
Mohammed S
MS
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Burshtyn
Deborah N
DN
Kane
Kevin P
KP
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D003602:Cytotoxicity, Immunologic; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases; D055630:Receptors, NK Cell Lectin-Like
D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly; D037181:Lectins, C-Type; D016169:Lymphocyte Function-Associated Antigen-1; D055630:Receptors, NK Cell Lectin-Like; C484963:Tyrobp protein, mouse; D018799:Intercellular Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases