Fischer April M, Katayama Carol D, Pagès Giles, Pouysségur Jacques, Hedrick Stephen M
Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0377, USA.
Immunity. 2005 Oct;23(4):431-43. doi: 10.1016/j.immuni.2005.08.013.
Activation of extracellular-signal-regulated protein kinase (Erk) is central to growth-factor-receptor-mediated signaling including that originating from the T cell antigen receptor. It integrates cytoplasmic signals to effect changes in transcription associated with differentiation, proliferation, and survival. In this report, we present an analysis of mice with targeted deletions in Erk1 and Erk2 to assess the relationship between Erk activity and cell-cycle progression, thymocyte development, and lineage commitment. These studies show that Erk is selectively retained during beta selection-driven proliferation, and yet Erk1/2 are not required to complete differentiation to CD4+CD8+ preselection stage of development. Erk activity is essential for the process of positive selection, and it differentially affects CD4 and CD8 T cell maturation; yet, diminished expression itself is not sufficient to alter lineage commitment.
细胞外信号调节蛋白激酶（Erk）的激活是生长因子受体介导信号传导的核心，包括源自T细胞抗原受体的信号传导。它整合细胞质信号以影响与分化、增殖和存活相关的转录变化。在本报告中，我们对Erk1和Erk2基因被靶向缺失的小鼠进行了分析，以评估Erk活性与细胞周期进程、胸腺细胞发育和谱系定向之间的关系。这些研究表明，在β选择驱动的增殖过程中，Erk被选择性保留，但完成向CD4+CD8+预选择发育阶段的分化并不需要Erk1/2。Erk活性对于阳性选择过程至关重要，并且它对CD4和CD8 T细胞成熟有不同影响；然而，其表达减少本身不足以改变谱系定向。
