A critical role for the cytoplasmic tail of pTα in T lymphocyte development
A critical role for the cytoplasmic tail of pTα in T lymphocyte development
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DOI：
10.1038/ni779
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发表时间：
2002-05-01
影响因子：
30.5
通讯作者：
von Boehmer, H
中科院分区：
文献类型：
--
作者：
Aifantis, I;Borowski, C;von Boehmer, H
来自T细胞前受体（pre-TCR）的信号调节了T细胞谱系发育所需的多个过程。与伽玛δ TCR相反，前TCR在膜筏上自主定位，在那里它似乎以一种组成和配体独立的方式发出信号。我们在这里讨论了前tcrα链（pTalpha）的细胞质结构域特有的结构特征所起的作用。更具体地说，我们研究了可能在信号转导中发挥作用的con -末端富含脯氨酸的序列，以及可能成为棕榈酰化目标的近膜半胱氨酸残基，从而允许自发筏定位。pTalpha突变体在转基因小鼠、逆转录病毒转导的T细胞前体和细胞系中的表达表明，pTalpha细胞质尾部，特别是富含脯氨酸的区域，在tcr前信号传导和T细胞发育中起着至关重要的作用。相反，pTalpha近膜半胱氨酸对于tcr前功能似乎是不可缺少的。
Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the alphabeta T cell lineage. In contrast to the gammadelta TCR, the pre-TCR localizes cellautonomously to membrane rafts, where it appears to signal in a constitutive and ligand-independent manner.We addressed here the role played by structural features specific to the cytoplasmic domain of the pre-TCRalpha chain (pTalpha). More specifically, we examined a COON-terminal proline-rich sequence that might play a role in signal transduction and a juxtamembrane cysteine residue that could be a target for palmitoylation, thus allowing spontaneous raft localization. Expression of pTalpha mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTalpha cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTalpha juxtamembrane cysteine appeared to be dispensable for pre-TCR function.