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Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.

Publication ,  Journal Article
Shapiro, MJ; Nguyen, CT; Aghajanian, H; Zhang, W; Shapiro, VS
Published in: J Immunol
November 15, 2008

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.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2008

Volume

181

Issue

10

Start / End Page

7055 / 7061

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Receptor Cross-Talk
  • Phosphotyrosine
  • Phosphorylation
  • Lymphocyte Activation
  • Jurkat Cells
  • Immunoprecipitation
 

Citation

APA
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MLA
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Shapiro, M. J., Nguyen, C. T., Aghajanian, H., Zhang, W., & Shapiro, V. S. (2008). Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms. J Immunol, 181(10), 7055–7061. https://doi.org/10.4049/jimmunol.181.10.7055
Shapiro, Michael J., Chau T. Nguyen, Haig Aghajanian, Weiguo Zhang, and Virginia Smith Shapiro. “Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.J Immunol 181, no. 10 (November 15, 2008): 7055–61. https://doi.org/10.4049/jimmunol.181.10.7055.
Shapiro MJ, Nguyen CT, Aghajanian H, Zhang W, Shapiro VS. Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms. J Immunol. 2008 Nov 15;181(10):7055–61.
Shapiro, Michael J., et al. “Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms.J Immunol, vol. 181, no. 10, Nov. 2008, pp. 7055–61. Pubmed, doi:10.4049/jimmunol.181.10.7055.
Shapiro MJ, Nguyen CT, Aghajanian H, Zhang W, Shapiro VS. Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms. J Immunol. 2008 Nov 15;181(10):7055–7061.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2008

Volume

181

Issue

10

Start / End Page

7055 / 7061

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Receptor Cross-Talk
  • Phosphotyrosine
  • Phosphorylation
  • Lymphocyte Activation
  • Jurkat Cells
  • Immunoprecipitation