| Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. | |
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MedLine Citation:
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PMID: 23154388 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Activating and inhibitory receptors control natural killer (NK) cell activity. T-cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) was recently identified as a new inhibitory receptor on T and NK cells that suppressed their effector functions. TIGIT harbors the immunoreceptor tail tyrosine (ITT)-like and ITIM motifs in its cytoplasmic tail. However, how its ITT-like motif functions in TIGIT-mediated negative signaling is still unclear. Here, we show that TIGIT/PVR (poliovirus receptor) engagement disrupts granule polarization leading to loss of killing activity of NK cells. The ITT-like motif of TIGIT has a major role in its negative signaling. After TIGIT/PVR ligation, the ITT-like motif is phosphorylated at Tyr225 and binds to cytosolic adapter Grb2, which can recruit SHIP1 to prematurely terminate phosphatidylinositol 3-kinase (PI3K) and MAPK signaling, leading to downregulation of NK cell function. In support of this, Tyr225 or Asn227 mutation leads to restoration of TIGIT/PVR-mediated cytotoxicity, and SHIP1 silencing can dramatically abolish TIGIT/PVR-mediated killing inhibition.Cell Death and Differentiation advance online publication, 16 November 2012; doi:10.1038/cdd.2012.141. |
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Authors:
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S Liu; H Zhang; M Li; D Hu; C Li; B Ge; B Jin; Z Fan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-16 |
Journal Detail:
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Title: Cell death and differentiation Volume: - ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. |
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