Fotini Gounari

Frederick Locke

Gregory Driessens

Judy L. Cannon

Schilham

Staal

Thomas F. Gajewski

Yan Zheng

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.</jats:p

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The Journal of Immunology

β-Catenin Inhibits T Cell Activation by Selective Interference with Linker for Activation of T Cells–Phospholipase C-γ1 Phosphorylation

β-Catenin Inhibits T Cell Activation by Selective Interference with Linker for Activation of T Cells–Phospholipase C-γ1 Phosphorylation

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