Interaction of Ras with P110γ Is Required for Thymic β-Selection in the Mouse
Interaction of Ras with P110γ Is Required for Thymic β-Selection in the Mouse
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DOI：
10.4049/jimmunol.1101949
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Turner, Martin
中科院分区：
文献类型：
--
作者：
Janas, Michelle L.;Turner, Martin
通过在称为β-选择的过程中表达前TCR来测试胸腺细胞的tcrb基因座的生产性重排，这需要Notch 1和CXCR 4信号传导。已经表明，GTCR Ras的激活允许胸腺细胞在没有Pre-TCR的情况下增殖和分化;然而，Ras在该检查点的直接靶点尚未确定。具有p110 γ突变等位基因的小鼠不能结合活性Ras，表明CXCR 4介导的PI 3 K活化是Ras依赖性的。Ras-p110 γ相互作用对于有效的β选择促进增殖是必要的，但是对于胸腺细胞的存活或分化是不必要的。从p110 g解偶联Ras提供了胸腺b-选择所需的Ras相互作用的明确鉴定。免疫学杂志，2011，187：4667-4675。
Thymocytes are tested for productive rearrangement of the tcrb locus by expression of a pre-TCR in a process termed beta-selection, which requires both Notch1 and CXCR4 signaling. It has been shown that activation of the GTPase Ras allows thymocytes to proliferate and differentiate in the absence of a Pre-TCR; the direct targets of Ras at this checkpoint have not been identified, however. Mice with a mutant allele of p110 gamma unable to bind active Ras revealed that CXCR4-mediated PI3K activation is Ras dependent. The Ras-p110 gamma interaction was necessary for efficient beta-selection-promoted proliferation but was dispensable for the survival or differentiation of thymocytes. Uncoupling Ras from p110g provides unambiguous identification of a Ras interaction required for thymic b-selection. The Journal of Immunology, 2011, 187: 4667-4675.