Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-γ1 phosphorylation.
Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-γ1 phosphorylation.
复制标题
DOI：
10.4049/jimmunol.1001562
复制
发表时间：
2011-01-15
期刊：
影响因子：
--
通讯作者：
Gajewski TF
中科院分区：
文献类型：
--
作者：
Driessens G;Zheng Y;Locke F;Cannon JL;Gounari F;Gajewski TF
尽管β-连环蛋白通路在胸腺细胞中的功能已明确，但其在外周T细胞中的功能作用仍知之甚少。我们报道了在小鼠模型中，β-连环蛋白在外周T细胞中组成性降解。将稳定的β-连环蛋白引入原代T细胞抑制TCR刺激后的增殖和细胞因子分泌，并钝化效应细胞分化。功能和生物化学研究表明，β-catenin选择性抑制T细胞酪氨酸136磷酸化的linker，这与磷脂酶C-γ1磷酸化缺陷和钙信号转导有关，但与正常的ERK激活有关。我们的研究结果表明，β-连环蛋白负调节T细胞活化的一个以前未描述的机制，并表明，条件下，β-连环蛋白可能是诱导稳定在体内将抑制T细胞为基础的免疫。
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.