The Non-Classical MAP Kinase ERK3 Controls T Cell Activation

The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4+ and CD8+ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation.经典丝裂原活化蛋白激酶（mitogen-activated protein kinases, MAPKs）ERK1与ERK2可被多种细胞外信号（包括抗原）刺激激活，进而介导细胞应答的发生。ERK3是MAPK家族的非典型成员，与ERK1/2的同源性最高。为此，我们评估了ERK3在成熟T细胞应答中的作用。小鼠静息T细胞不转录ERK3基因，但在T细胞受体（T cell receptor, TCR）介导的T细胞活化后，CD4+与CD8+ T细胞中ERK3的表达均被诱导。T淋巴细胞中ERK3表达的诱导依赖于经典MAPK ERK1与ERK2的活化。此外，在活化的原代T细胞中，ERK3蛋白会发生磷酸化并与MK5结合。我们的研究表明，ERK3缺陷型T细胞的增殖速率降低，且在体外经低剂量抗CD3抗体刺激后，其细胞因子分泌功能受损。本研究证实，非典型MAPK ERK3是TCR诱导的T细胞活化的新型重要调控因子。