CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling
CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling
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DOI：
10.1038/ni877
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发表时间：
2003-02-01
影响因子：
30.5
通讯作者：
Acuto, O
中科院分区：
文献类型：
--
作者：
Irles, C;Symons, A;Acuto, O
跨膜磷酸酶CD45调节LCK活性和T细胞受体(TCR)信号转导。在这里，我们测试了CD45的大的胞外结构域是否在这一调控中发挥作用。含有CD43大胞外区的CD45嵌合体可以有效地挽救CD45缺失T细胞中的TCR信号，而含有其他磷酸酶的小胞外区的CD45嵌合体则不能。未受刺激的细胞的基础LCK活性和TCR诱导的TCR Zeta链酪氨酸磷酸化和LCK活性的增加都依赖于具有较大胞外结构域的CD45的表达。与含有小胞外结构域的CD45嵌合体不同，具有大胞外结构域的CD45嵌合体和野生型CD45本身都部分定位于神经鞘糖脂富集膜(GEM)。综上所述，这些数据表明，大的CD45胞外结构域是优化TCR信号所必需的。
The transmembrane phosphatase CD45 regulates both Lck activity and T cell receptor (TCR) signaling. Here we have tested whether the large ectodomain of CD45 has a role in this regulation. A CD45 chimera containing the large ectodomain of CD43 efficiently rescues TCR signaling in CD45-null T cells, whereas CD45 chimeras containing small ectodomains from other phosphatases do not. Both basal Lck activity in unstimulated cells and the TCR-induced increase in tyrosine phosphorylation of the TCR zeta-chain and in Lck activity depend on the expression of CD45 with a large ectodomain. Unlike CD45 chimeras containing small ectodomains, both the CD45 chimera with a large ectodomain and wild-type CD45 itself are partially localized to glycosphingolipid-enriched membranes (GEMs). Taken together, these data show that the large CD45 ectodomain is required for optimal TCR signaling.