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A critical role for the cytoplasmic tail of pTα in T lymphocyte development

机译:pTα的细胞质尾巴在T淋巴细胞发育中的关键作用

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Signals that emanate from the pre-T cell receptor (pre-TCR) regulate multiple processes required for the development of the αβT cell lineage. In contrast to the γδTCR, the pre-TCR localizes cell-autonomously 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-TCRα chain (pTα). More specifically, we examined a COOH-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 pTα mutants in transgenic mice, retrovirally transduced T cell precursors and cell lines showed that the pTα cytoplasmic tail, in particular the proline-rich domain, plays a crucial role in pre-TCR signaling and T cell development. In contrast, the pTα juxtamembrane cysteine appeared to be dispensable for pre-TCR function.
机译:从前T细胞受体(pre-TCR)发出的信号调节着αβT细胞谱系发育所需的多个过程。与γδTCR相比,pre-TCR自主地将细胞定位在膜筏上,在那里它似乎以本构且不依赖配体的方式发出信号。我们在这里讨论了特异于TCRα前链(pTα)胞质结构域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起作用的富含COOH末端脯氨酸的序列以及可能成为棕榈酰化靶标的近膜半胱氨酸残基,从而实现了自发的筏定位。 pTα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,pTα胞质尾巴,特别是富含脯氨酸的域,在TCR前信号传导和T细胞发育中起着关键作用。相反,pTα近膜半胱氨酸似乎对TCR前功能不可或缺。

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