Department of Cell Biology and Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, United States of America.
PLoS One. 2010 Nov 10;5(11):e15425. doi: 10.1371/journal.pone.0015425.
T lymphocytes play a critical role in cell-mediated immune responses. During activation, extracellular and intracellular signals alter T cell metabolism in order to meet the energetic and biosynthetic needs of a proliferating, active cell, but control of these phenomena is not well defined. Previous studies have demonstrated that signaling from the costimulatory receptor CD28 enhances glucose utilization via the phosphatidylinositol-3-kinase (PI3K) pathway. However, since CD28 ligation alone does not induce glucose metabolism in resting T cells, contributions from T cell receptor-initiated signaling pathways must also be important. We therefore investigated the role of mitogen-activated protein kinase (MAPK) signaling in the regulation of mouse T cell glucose metabolism. T cell stimulation strongly induces glucose uptake and glycolysis, both of which are severely impaired by inhibition of extracellular signal-regulated kinase (ERK), whereas p38 inhibition had a much smaller effect. Activation also induced hexokinase activity and expression in T cells, and both were similarly dependent on ERK signaling. Thus, the ERK signaling pathway cooperates with PI3K to induce glucose utilization in activated T cells, with hexokinase serving as a potential point for coordinated regulation.
T 淋巴细胞在细胞介导的免疫反应中发挥着关键作用。在激活过程中，细胞外和细胞内信号改变 T 细胞代谢，以满足增殖、活跃细胞的能量和生物合成需求，但这些现象的控制尚不清楚。先前的研究表明，共刺激受体 CD28 的信号通过磷脂酰肌醇-3-激酶（PI3K）途径增强葡萄糖利用。然而，由于 CD28 单独结合并不能诱导静止 T 细胞中的葡萄糖代谢，因此 T 细胞受体起始信号通路的贡献也必须很重要。因此，我们研究了丝裂原活化蛋白激酶（MAPK）信号在调节小鼠 T 细胞葡萄糖代谢中的作用。T 细胞刺激强烈诱导葡萄糖摄取和糖酵解，这两者都被细胞外信号调节激酶（ERK）抑制剂严重抑制，而 p38 抑制剂的作用要小得多。激活还诱导 T 细胞中己糖激酶的活性和表达，两者都同样依赖于 ERK 信号。因此，ERK 信号通路与 PI3K 合作诱导激活的 T 细胞中葡萄糖的利用，己糖激酶作为协调调节的潜在点。
