Document Detail


Cutting edge: The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse.
MedLine Citation:
PMID:  20962259     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
EWS/FLI1-activated transcript 2 (EAT-2)A and EAT-2B are single SH2-domain proteins, which bind to phosphorylated tyrosines of signaling lymphocyte activation molecule family receptors in murine NK cells. While EAT-2 is a positive regulator in human cells, a negative regulatory role was attributed to the adapter in NK cells derived from EAT-2A-deficient 129Sv mice. To evaluate whether the genetic background or the presence of a selection marker in the mutant mice could influence the regulatory mode of these adapters, we generated EAT-2A-, EAT-2B-, and EAT-2A/B-deficient mice using C57BL/6 embryonic stem cells. We found that NK cells from EAT-2A- and EAT-2A/B-deficient mice were unable to kill tumor cells in a CD244- or CD84-dependent manner. Furthermore, EAT-2A/B positively regulate phosphorylation of Vav-1, which is known to be implicated in NK cell killing. Thus, as in humans, the EAT-2 adapters act as positive regulators of signaling lymphocyte activation molecule family receptor-specific NK cell functions in C57BL/6 mice.
Authors:
Ninghai Wang; Silvia Calpe; Jill Westcott; Wilson Castro; Chunyan Ma; Pablo Engel; John D Schatzle; Cox Terhorst
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-20
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2010-12-02     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5683-7     Citation Subset:  AIM; IM    
Affiliation:
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. nwang@bidmc.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing
Animals
Antigens, CD / immunology*
Blotting, Western
Cell Separation
Cytotoxicity, Immunologic
Flow Cytometry
Immunoprecipitation
Killer Cells, Natural / immunology*
Lymphocyte Activation / immunology*
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Receptors, Immunologic / immunology*
Transcription Factors / immunology*
Grant Support
ID/Acronym/Agency:
AI067803/AI/NIAID NIH HHS; P01 AI-065687/AI/NIAID NIH HHS; P01 AI065687-01A1/AI/NIAID NIH HHS; R01 AI067803-01A2/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Antigens, CD; 0/Cd244 protein, mouse; 0/Cd84 protein, mouse; 0/Receptors, Immunologic; 0/Sh2d1b1 protein, mouse; 0/Transcription Factors
Comments/Corrections

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