Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge CB22 3AT, United Kingdom.
J Immunol. 2011 Nov 1;187(9):4667-75. doi: 10.4049/jimmunol.1101949. Epub 2011 Sep 19.
Thymocytes are tested for productive rearrangement of the tcrb locus by expression of a pre-TCR in a process termed β-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 p110γ unable to bind active Ras revealed that CXCR4-mediated PI3K activation is Ras dependent. The Ras-p110γ interaction was necessary for efficient β-selection-promoted proliferation but was dispensable for the survival or differentiation of thymocytes. Uncoupling Ras from p110γ provides unambiguous identification of a Ras interaction required for thymic β-selection.
胸腺细胞通过表达前 T 细胞受体（Pre-TCR）进行 TCRβ 基因座的有效重排，这个过程称为β选择，需要 Notch1 和 CXCR4 信号。已经表明，GTP 酶 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，在此检查点，Ras 的直接靶标尚未确定。缺乏能够结合活性 Ras 的 p110γ 突变等位基因的小鼠表明，CXCR4 介导的 PI3K 激活依赖于 Ras。Ras-p110γ 相互作用对于有效的β选择促进增殖是必需的，但对于胸腺细胞的存活或分化是可有可无的。将 Ras 与 p110γ 分离提供了对胸腺β选择所必需的 Ras 相互作用的明确鉴定。
