Research ArticleImmunology

Dephosphorylation of the adaptor LAT and phospholipase C–γ by SHP-1 inhibits natural killer cell cytotoxicity

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Science Signaling  24 May 2016:
Vol. 9, Issue 429, pp. ra54
DOI: 10.1126/scisignal.aad6182

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Keeping NK cells in check

Natural killer (NK) cells are immune cells that recognize and kill virally infected cells and tumor cells. Whether an NK cell becomes activated or inhibited depends on the relative extent of signaling by cell surface activating or inhibitory receptors that are engaged. Inhibitory receptor signaling activates the inhibitory phosphatase SHP-1. In experiments with human NK cells, Matalon et al. identified the adaptor protein LAT and two members of the phospholipase C–γ family as substrates of SHP-1. Inhibitory receptor signaling not only resulted in dephosphorylation of LAT, which reduced intracellular Ca2+ signaling by activating receptors, but also promoted LAT ubiquitylation and degradation, further dampening NK cell function.

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