Document Detail


Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.
MedLine Citation:
PMID:  18981125     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The activation of T cells and the initiation of an immune response is tightly controlled through the crosstalk of both positive and negative regulators. Two adaptors that function as negative regulators of T cell activation are adaptor in lymphocytes of unknown function X (ALX) and linker for activation of X cell (LAX). Previously, we showed that T cells from mice deficient in ALX and LAX display similar hyperresponsiveness, with increased IL-2 production and proliferation upon TCR/CD28 stimulation, and that these adaptors physically associate. In this study, we analyze the nature of the association between ALX and LAX. We demonstrate that this association occurs in the absence of TCR/CD28 signaling via a mechanism independent of both tyrosine phosphorylation of LAX and the SH2 domain of ALX. Cotransfection of ALX with LAX resulted in LAX tyrosine phosphorylation in the absence of TCR/CD28 stimulation. ALX-mediated LAX phosphorylation depends upon the ALX SH2 domain, which functions to recruit Lck to LAX. We also show that LAX, like ALX, can inhibit RE/AP reporter activation. However, in contrast to its inhibition of NFAT, the inhibition of RE/AP by LAX is independent of its tyrosine phosphorylation. Therefore, it can be concluded that inhibition of signaling events involved in T cell activation by LAX occurs through mechanisms both dependent on and independent of its tyrosine phosphorylation.
Authors:
Michael J Shapiro; Chau T Nguyen; Haig Aghajanian; Weiguo Zhang; Virginia Smith Shapiro
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2008-12-12     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7055-61     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics,  immunology,  metabolism*
Adaptor Proteins, Vesicular Transport / genetics,  immunology,  metabolism*
Antigens, CD28 / immunology,  metabolism
Humans
Immunoblotting
Immunoprecipitation
Jurkat Cells
Lymphocyte Activation / immunology*
Phosphorylation
Phosphotyrosine / metabolism
Receptor Cross-Talk / immunology
Receptors, Antigen, T-Cell / immunology,  metabolism*
Signal Transduction / immunology*
T-Lymphocytes / immunology,  metabolism*
Transfection
Grant Support
ID/Acronym/Agency:
R01 AI048674/AI/NIAID NIH HHS; R01 AI054974/AI/NIAID NIH HHS; R01 AI054974/AI/NIAID NIH HHS; R01 AI054974-05/AI/NIAID NIH HHS; R01 AI054974-06/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Adaptor Proteins, Vesicular Transport; 0/Antigens, CD28; 0/HSH2D protein, human; 0/LAX1 protein, human; 0/Receptors, Antigen, T-Cell; 21820-51-9/Phosphotyrosine
Comments/Corrections

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