β-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-γ1 phosphorylation

Gregory Driessens, Yan Zheng, Frederick Locke, Judy L. Cannon, Fotini Gounari, Thomas F. Gajewski

Research output: Contribution to journalArticlepeer-review

Abstract

Despite the defined function of the β-catenin pathway in thymocytes, its functional role in peripheral T cells is poorly understood. We report that in a mouse model, β-catenin protein is constitutively degraded in peripheral T cells. Introduction of stabilized β-catenin into primary T cells inhibited proliferation and cytokine secretion after TCR stimulation and blunted effector cell differentiation. Functional and biochemical studies revealed that β-catenin selectively inhibited linker for activation of T cells phosphorylation on tyrosine 136, which was associated with defective phospholipase C-γ1 phosphorylation and calcium signaling but normal ERK activation. Our findings indicate that β-catenin negatively regulates T cell activation by a previously undescribed mechanism and suggest that conditions under which β-catenin might be inducibly stabilized in vivo would be inhibitory for T cell-based immunity.

Original languageEnglish (US)
Pages (from-to)784-790
Number of pages7
JournalJournal of Immunology
Volume186
Issue number2
DOIs
StatePublished - Jan 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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