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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MAP kinase phosphatase activity sets the threshold for thymocyte positive selection
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MAP kinase phosphatase activity sets the threshold for thymocyte positive selection

机译：MAP激酶磷酸酶活性为胸腺细胞阳性选择设定阈值

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摘要

Phosphorylation of MAP kinases is important for proper translation of T cell antigen receptor (TCR) signals into thymocyte cell fates, but the role of MAP kinase phosphatase (MKP) activity in thymocyte development has not been characterized. To explore the role of MKP in thymocytes, we constructed a double mutant MKP-3 (DM-MKP3) that acts as a dominant-negative inhibitor of ERK- and JNK-specific MKP. Thymocytes developing in the presence of DM-MKP3 have enhanced frequencies of both CD4 and CD8 mature, single-positive cells and no increase in apoptosis. Expression of DM-MKP3 also results in an increased proportion of thymocytes with high levels of both CD69 and TCRβ, suggesting that the increased proportion of mature thymocytes is the result of an increased probability that CD4~+ CD8~+ cells will be positively selected. Thus, MKP activity controls thymocyte cell fate by regulating the threshold of TCR signaling that is able to induce positive selection.
机译：MAP激酶的磷酸化对于T细胞抗原受体（TCR）信号向胸腺细胞命运的正确翻译很重要，但是尚未鉴定MAP激酶磷酸酶（MKP）活性在胸腺细胞发育中的作用。为了探索MKP在胸腺细胞中的作用，我们构建了一个双重突变体MKP-3（DM-MKP3），可作为ERK和JNK特异性MKP的显性负抑制剂。在存在DM-MKP3的情况下发育的胸腺细胞的CD4和CD8成熟单阳性细胞的频率均增加，并且凋亡没有增加。 DM-MKP3的表达也会导致胸腺细胞中CD69和TCRβ含量较高的比例增加，这表明成熟胸腺细胞比例的增加是CD4〜+ CD8〜+细胞被积极选择的可能性增加的结果。因此，MKP活性通过调节能够诱导阳性选择的TCR信号传导阈值来控制胸腺细胞的命运。

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