CD45 ectodomain controls interaction with GEMs and Lck activity for optimal TCR signaling

被引：143
作者：
Irles, C
Symons, A
Michel, F
Bakker, TR
van der Merwe, PA
Acuto, O
机构：
[1] Inst Pasteur, Dept Immunol, Mol Immunol Unit, F-75724 Paris 15, France
[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England
来源：
NATURE IMMUNOLOGY | 2003年 / 4卷 / 02期
基金：
英国医学研究理事会;
关键词：
D O I：
10.1038/ni877
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：189 / 197
页数：9
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