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Publication : Activating Ly-49 receptors regulate LFA-1-mediated adhesion by NK cells.

First Author  Osman MS Year  2007
Journal  J Immunol Volume  178
Issue  3 Pages  1261-7
PubMed ID  17237371 Mgi Jnum  J:143665
Mgi Id  MGI:3828385 Doi  10.4049/jimmunol.178.3.1261
Citation  Osman MS, et al. (2007) Activating Ly-49 receptors regulate LFA-1-mediated adhesion by NK cells. J Immunol 178(3):1261-7
abstractText  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.
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