2. Academic Validation
  3. An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells

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.
Ming-Can Yu 1,  Liu-Li Su,  Lin Zou,  Ye Liu,  Na Wu,  Ling Kong,  Zi-Heng Zhuang,  Lei Sun,  Hai-Peng Liu,  Jun-Hao Hu,  Dangsheng Li,  Jack L Strominger,  Jing-Wu Zang,  Gang Pei,  Bao-Xue Ge
Affiliations

Affiliation

  • 1 Laboratory of Signal Transduction, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
PMID: 18604210 DOI: 10.1038/ni.1635
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.

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