An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.
Article Details
- CitationCopy to clipboard
Yu MC, Su LL, Zou L, Liu Y, Wu N, Kong L, Zhuang ZH, Sun L, Liu HP, Hu JH, Li D, Strominger JL, Zang JW, Pei G, Ge BX
An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.
Nat Immunol. 2008 Aug;9(8):898-907. doi: 10.1038/ni.1635. Epub 2008 Jul 11.
- PubMed ID
- 18604210 [ View in PubMed]
- Abstract
The inhibitory signaling of natural killer (NK) cells is crucial in the regulation of innate immune responses. Here we show that the association of KIR2DL1, an inhibitory receptor of NK cells, with beta-arrestin 2 mediated recruitment of the tyrosine phosphatases SHP-1 and SHP-2 to KIR2DL1 and facilitated 'downstream' inhibitory signaling. Consequently, the cytotoxicity of NK cells was higher in beta-arrestin 2-deficient mice but was inhibited in beta-arrestin 2-transgenic mice. Moreover, beta-arrestin 2-deficient mice were less susceptible than wild-type mice to mouse cytomegalovirus infection, an effect that was abolished by depletion of NK cells. Our findings identify a previously unknown mechanism by which the inhibitory signaling in NK cells is regulated.