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

Michael J. Shapiro, Chau T. Nguyen, Haig Aghajanian, Weiguo Zhang, Virginia M Shapiro

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7055-7061
Number of pages7
JournalJournal of Immunology
Volume181
Issue number10
StatePublished - Nov 15 2008

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Phosphotyrosine
Phosphorylation
Tyrosine
T-Lymphocytes
src Homology Domains
Interleukin-2
Lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms. / Shapiro, Michael J.; Nguyen, Chau T.; Aghajanian, Haig; Zhang, Weiguo; Shapiro, Virginia M.

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 7055-7061.

Research output: Contribution to journalArticle

Shapiro, Michael J. ; Nguyen, Chau T. ; Aghajanian, Haig ; Zhang, Weiguo ; Shapiro, Virginia M. / Negative regulation of TCR signaling by linker for activation of X cells via phosphotyrosine-dependent and -independent mechanisms. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 7055-7061.
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