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

Despite the defined function of the beta-catenin pathway in thymocytes, its functional role in peripheral T cells is poorly understood. We report that in a mouse model, beta-catenin protein is constitutively degraded in peripheral T cells. Introduction of stabilized b-catenin into primary T cells inhibited proliferation and cytokine secretion after TCR stimulation and blunted effector cell differentiation. Functional and biochemical studies revealed that beta-catenin selectively inhibited linker for activation of T cells phosphorylation on tyrosine 136, which was associated with defective phospholipase C-gamma 1 phosphorylation and calcium signaling but normal ERK activation. Our findings indicate that beta-catenin negatively regulates T cell activation by a previously undescribed mechanism and suggest that conditions under which beta-catenin might be inducibly stabilized in vivo would be inhibitory for T cell-based immunity. The Journal of Immunology, 2011, 186: 784-790.