title: An essential function for beta-arrestin 2 in the inhibitory signaling of natural killer cells.
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.
authors.affiliation: Laboratory of Signal Transduction, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Ming-Can
authors.initials: MC
authors.lastname: Yu
authors.forename: Liu-Li
authors.initials: LL
authors.lastname: Su
authors.forename: Lin
authors.initials: L
authors.lastname: Zou
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.forename: Ling
authors.initials: L
authors.lastname: Kong
authors.forename: Zi-Heng
authors.initials: ZH
authors.lastname: Zhuang
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Liu
authors.forename: Jun-Hao
authors.initials: JH
authors.lastname: Hu
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
authors.forename: Jing-Wu
authors.initials: JW
authors.lastname: Zang
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
authors.forename: Bao-Xue
authors.initials: BX
authors.lastname: Ge
mesh_terms: 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
chemical_list: C000605258:Arrb2 protein, mouse; D019390:Arrestins; D047908:Intracellular Signaling Peptides and Proteins; D011971:Receptors, Immunologic; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins