Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development
Cbp deficiency alters Csk localization in lipid rafts but does not affect T-cell development
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DOI：
10.1128/mcb.25.19.8486-8495.2005
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发表时间：
2005-10-01
影响因子：
5.3
通讯作者：
Lam, KP
中科院分区：
文献类型：
--
作者：
Xu, SL;Huo, HX;Lam, KP
普遍表达的跨膜接头 Csk 结合蛋白 (Cbp) 将 Csk 募集至脂筏，后者对蛋白酪氨酸激酶 Src 家族发挥负调节作用。我们已经灭活了小鼠种系中的 Cbp。 Csk 基因失活会导致胚胎死亡和 T 细胞发育受损，与此相反，Cbp 缺陷小鼠能够存活并表现出正常的 T 细胞发育，但胸腺细胞数量增加。在没有 Cbp 的情况下，定位于脂筏的 Csk 量大大减少。有趣的是，这种 Csk 脂筏定位的改变并没有导致 T 细胞出现任何可检测到的生化或功能缺陷。 T细胞受体诱导的细胞内钙流、细胞增殖和细胞因子分泌不受Cbp缺失的影响。在 Cbp 缺陷小鼠中，外周 T 细胞对超抗原 SEB 的耐受性也基本保持完整。因此，Cbp 对于 T 细胞的发育和激活来说是可有可无的。
The ubiquitously expressed transmembrane adaptor Csk-binding protein (Cbp) recruits Csk to lipid rafts, where the latter exerts its negative regulatory effect on the Src family of protein tyrosine kinases. We have inactivated Cbp in the mouse germ line. In contrast to Csk gene inactivation, which leads to embryonic lethality and impaired T-cell development, Cbp-deficient mice were viable and exhibited normal T-cell development but with an increased thymocyte population. In the absence of Cbp, the amount of Csk that localizes to the lipid rafts was greatly reduced. Interestingly, this altered lipid raft localization of Csk did not lead to any detectable biochemical or functional defect in T cells. The T-cell receptor-induced intracellular calcium flux, cell proliferation, and cytokine secretion were not affected by the absence of Cbp. Peripheral T-cell tolerance to superantigen SEB was also largely intact in Cbp-deficient mice. Thus, Cbp is dispensable for T-cell development and activation.