The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling
The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling
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DOI：
10.1073/pnas.94.18.9797
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Pawson, T
中科院分区：
文献类型：
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作者：
Cheng, AM;Negishi, I;Pawson, T
胸腺细胞发育的早期阶段，在 T 细胞受体 (TCR) 的 β 链基因重排后，涉及前 TCR 复合物的表达以及伴随的 CD4(-)CD8(-) 双阴性 (DN) 细胞向 CD4(+)CD8(+) 双阳性 (DP) 细胞的分化。 ZAP-70 和 Syk 酪氨酸激酶各自包含两个 N 末端 SH2 结构域，可结合抗原受体亚基中的磷酸化基序，并参与前 T 受体信号传导。然而，缺乏 ZAP-70 或 Syk 的小鼠在 DP 胸腺细胞的形成方面没有缺陷。在这里，我们表明，在同时缺乏 Syk 和 ZAP-70 的小鼠中，DN 胸腺细胞经历 β 链基因重排，但无法启动克隆扩增，并且在表达前 TCR 后无法分化为 DP 细胞。这些数据表明，ZAP-70 和 Syk 酪氨酸激酶在来自前 TCR 的信号传导中具有重要但重叠的功能，因此在早期胸腺细胞发育中。
An early stage in thymocyte development, after rearrangement of the beta chain genes of the T cell receptor (TCR), involves expression of the pre-TCR complex and accompanying differentiation of CD4(-)CD8(-) double negative (DN) cells to CD4(+)CD8(+) double positive (DP) cells. The ZAP-70 and Syk tyrosine kinases each contain two N-terminal SH2 domains that bind phosphorylated motifs in antigen receptor subunits and are implicated in pre-T receptor signaling. However, mice deficient in either ZAP-70 or Syk have no defect in the formation of DP thymocytes. Here we show that, in mice lacking both Syk and ZAP-70, DN thymocytes undergo beta chain gene rearrangement but fail to initiate clonal expansion and are incapable of differentiating into DP cells after expression of the pre-TCR These data suggest that the ZAP-70 and Syk tyrosine kinases have crucial but overlapping functions in signaling from the pre-TCR and hence in early thymocyte development.