Shao H, Rubin E M, Chen L Y, Kaye J
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Immunol. 1997 Dec 15;159(12):5773-6.
Evidence suggests that the Ras/mitogen-activated protein kinase signaling pathway is required for positive selection of thymocytes. We have asked whether Ras activation is also sufficient to mediate changes in gene expression that are associated with positive selection. To accomplish this, we expressed a constitutively active form of Ras in the immature CD4+ 8+ DPK thymocyte cell line. DPK cells that express active Ras have reduced levels of CD8alpha and CD8beta at the level of cell surface protein and mRNA. These data provide evidence of a direct link between Ras signaling pathways and coreceptor regulation during positive selection. They also suggest that a sustained or potent Ras signal may play a critical role in directing thymocytes into the CD4 lineage. DPK cells that express active Ras, however, were not fully differentiated, indicating that Ras signaling provides only a partial signal for double-positive thymocyte differentiation.
有证据表明，Ras/丝裂原活化蛋白激酶信号通路是胸腺细胞阳性选择所必需的。我们探讨了Ras激活是否也足以介导与阳性选择相关的基因表达变化。为实现这一点，我们在未成熟的CD4+8+DPK胸腺细胞系中表达了一种组成型激活形式的Ras。表达活性Ras的DPK细胞在细胞表面蛋白和mRNA水平上CD8α和CD8β的水平降低。这些数据提供了阳性选择过程中Ras信号通路与共受体调节之间直接联系的证据。它们还表明，持续或强效的Ras信号可能在引导胸腺细胞进入CD4谱系中起关键作用。然而，表达活性Ras的DPK细胞并未完全分化，这表明Ras信号仅为双阳性胸腺细胞分化提供了部分信号。
