The influence of the MAPK pathway on T cell lineage commitment
The influence of the MAPK pathway on T cell lineage commitment
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DOI：
10.1016/s1074-7613(00)80382-9
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发表时间：
1997-11-01
期刊：
影响因子：
32.4
通讯作者：
Hedrick, SM
中科院分区：
文献类型：
--
作者：
Sharp, LL;Schwarz, DA;Hedrick, SM
在发育过程中，胸腺祖细胞分化为CD4或CD8 T细胞，并且这种命运决定取决于T细胞抗原受体（TCR）对MHC II类或I类分子的特异性。基于已知的简单后生动物生物体的命运特化机制，我们试图确定细胞外信号相关激酶（ERK）是否在T细胞分化和谱系定型中发挥作用。使用erk2基因的显性功能获得性突变体，我们表明分化为CD4谱系是有利的。我们还表明，相反，添加ERK通路的药理学抑制剂有利于分化为CD8谱系。我们提出了一个定量选择模型，结合这些结果，以及最近的报告中的作用，Notch在T细胞谱系规范。
During development, progenitor thymocytes differentiate into either CD4 or CD8 T cells, and this fate decision depends on the specificity of the T cell antigen receptor (TCR) for MHC class II or class I molecules. Based on the mechanisms of fate specification known for simple metazoan organisms, we sought to determine whether the extracellular signal-related kinases (ERKs) play a role in T cell differentiation and lineage commitment. Using a dominant gain-of-function mutant of the erk2 gene, we show that differentiation into the CD4 lineage is favored. We also show that, conversely, the addition of a pharmacological inhibitor of the ERK pathway favors differentiation into the CD8 lineage. We present a quantitative selection model that incorporates these results as well as those of recent reports on the role of Notch in T cell lineage specification.