Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Trends Immunol. 2013 Jun;34(6):259-68. doi: 10.1016/j.it.2013.02.004. Epub 2013 Mar 15.
Extracellular signal-regulated kinase (ERK) activation is important for both thymocyte development and T cell function. Classically, signal transduction from the T cell antigen receptor (TCR) to ERK is thought to be regulated by signaling from Ras guanine nucleotide exchange factors (GEFs), through the small G protein Ras, to the three-tiered Raf-MAPK/ERK kinase (MEK)-ERK kinase cascade. Developing and mature T cells express four members of two RasGEF families, RasGRP1, RasGRP4, son of sevenless 1 (Sos1), and Sos2, and several models describing combined signaling from these RasGEFs have been proposed. However, recent studies suggest that existing models need revision to include both distinct and overlapping roles of multiple RasGEFs during thymocyte development and novel, Ras-independent signals to ERK that have been identified in peripheral T cells.
细胞外信号调节激酶（ERK）的激活对于胸腺细胞的发育和 T 细胞的功能都很重要。传统上，T 细胞抗原受体（TCR）到 ERK 的信号转导被认为是通过 Ras 鸟嘌呤核苷酸交换因子（GEF）的信号来调节的，通过小 G 蛋白 Ras 到三磷酸化 Raf-MAPK/ERK 激酶（MEK）-ERK 激酶级联。发育中的和成熟的 T 细胞表达两个 RasGEF 家族的四个成员，RasGRP1、RasGRP4、Sos1 和 Sos2，并且已经提出了几种描述这些 RasGEF 联合信号的模型。然而，最近的研究表明，现有的模型需要修订，以包括在胸腺细胞发育过程中多个 RasGEF 的独特和重叠作用，以及在周围 T 细胞中发现的新型、独立于 Ras 的 ERK 信号。
