Article abstract
Nature Immunology 9, 898 - 907 (2008)
Published online: 11 July 2008 | doi:10.1038/ni.1635
An essential function for
-arrestin 2 in the inhibitory signaling of natural killer cells
Ming-Can Yu1, Liu-Li Su1, Lin Zou2, Ye Liu1, Na Wu1, Ling Kong1,3, Zi-Heng Zhuang1,3, Lei Sun1,3, Hai-Peng Liu1, Jun-Hao Hu1, Dangsheng Li4, Jack L Strominger5, Jing-Wu Zang4, Gang Pei2 & Bao-Xue Ge1
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
-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
-arrestin 2–deficient mice but was inhibited in
-arrestin 2–transgenic mice. Moreover,
-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.
- Laboratory of Signal Transduction, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
- Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Graduate School of Chinese Academy of Sciences, Shanghai 200025, China.
- Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Correspondence to: Bao-Xue Ge1 e-mail: gebaoxue@sibs.ac.cn
Correspondence to: Gang Pei2 e-mail: gpei@sibs.ac.cn
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