Tec protein-tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain.
Tec protein-tyrosine kinase directly associates with Lyn protein-tyrosine kinase through its N-terminal unique domain.
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Tec 蛋白酪氨酸激酶通过其 N 端独特结构域直接与 Lyn 蛋白酪氨酸激酶结合。
作者：
H. Mano;K. Sato;Y. Yazaki;H. Hirai
大多数非受体型蛋白酪氨酸激酶具有共同的结构，例如N端独特结构域、Src同源区(SH)-2结构域、SH-3结构域和激酶结构域。尽管付出了大量的努力已经获得了一些有关 SH-2、-3 和激酶结构域的体内作用的信息，但对于 N 端独特结构域的功能仍然知之甚少。通过利用谷胱甘肽 S-转移酶 (GST) 融合系统，我们研究了 Tec 蛋白酪氨酸激酶 N 末端独特结构域在小鼠 IL-3 依赖性骨髓细胞系中的作用。我们可以揭示 Tec N 端独特结构域（NTec2 区域）的 C 端部分可以在体外以 IL-3 依赖性方式结合一组酪氨酸磷酸化细胞蛋白。令人惊讶的是，p56/53Lyn 与 NTec2 区域组成型结合。在 NTec2 结合的 Lyn 蛋白中，似乎只有 p56 形式可响应 IL-3 诱导酪氨酸磷酸化。 Lyn 与 NTec2 区域的结合域位于其 SH-3 域。 Tec 还被证明可以在体内与 Lyn 形成稳定的复合物。这是第一份证明不同细胞质蛋白酪氨酸激酶之间直接关联的报告，特别是通过 N 端独特结构域。
Most of non-receptor-type protein-tyrosine kinases share common structures, such as N-terminal unique domains, Src homology region (SH)-2 domains, SH-3 domains and kinase domains. Although vast effort has brought some information about the in vivo roles of SH-2, -3 and kinase domains, little is still understood about the function of N-terminal unique domain. By utilizing the glutathione S-transferase (GST)-fusion system, we have investigated the role of N-terminal unique domain of the Tec protein-tyrosine kinase in a mouse IL-3-dependent myeloid cell line. We could reveal that the C-terminal half of the Tec N-terminal unique domain (NTec2 region) can bind to a set of tyrosine-phosphorylated cellular proteins in vitro in an IL-3-dependent manner. Surprisingly, p56/53Lyn constitutively binds to the NTec2 region. Among the NTec2-bound Lyn proteins, only the p56 form seems to be inducibly tyrosine-phosphorylated in response to IL-3. Binding domain of Lyn to the NTec2 region was localized to its SH-3 domain. Tec was also shown to make a stable complex with Lyn in vivo. This is the first report demonstrating the direct association between distinct cytoplasmic protein-tyrosine kinases, especially through N-terminal unique domain.