An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.
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.
Yu
Ming-Can
MC
Laboratory of Signal Transduction, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
Su
Liu-Li
LL
Zou
Lin
L
Liu
Ye
Y
Wu
Na
N
Kong
Ling
L
Zhuang
Zi-Heng
ZH
Sun
Lei
L
Liu
Hai-Peng
HP
Hu
Jun-Hao
JH
Li
Dangsheng
D
Strominger
Jack L
JL
Zang
Jing-Wu
JW
Pei
Gang
G
Ge
Bao-Xue
BX
D000818:Animals; D019390:Arrestins / Q000494:pharmacology*; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605258:Arrb2 protein, mouse; D019390:Arrestins; D047908:Intracellular Signaling Peptides and Proteins; D011971:Receptors, Immunologic; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins