Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK
Tec tyrosine kinase links the cytokine receptors to PI-3 kinase probably through JAK
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Tec 酪氨酸激酶可能通过 JAK 将细胞因子受体与 PI-3 激酶连接起来
作者：
M. Takahashi;M. Hibi;Y. Fujitani;T. Fukada;Takuya Yamaguchi;T. Hirano
Tec/Btk酪氨酸激酶是Src酪氨酸激酶家族的一个亚组。据报道，它们响应于细胞因子如IL-3和IL-6而被激活。已知Janus激酶（JAK）与某些细胞因子受体例如gpl30（IL-6受体的信号转导亚基）和IL-3受体的共同β链相关，其可以在响应于细胞因子的受体二聚化时被激活。在这里，我们显示了Jak1/Jak2和Tec或Jak1和Btk之间的关联。此外，Jak1而不是Jak2诱导Btk的酪氨酸磷酸化，而不是Tec。这些观察结果表明，在细胞因子刺激后，JAK激活Tec/Btk或诱导其二聚化，导致内源性酪氨酸磷酸化。此外，使用酵母双杂交系统，我们已经确定了Tec，PI-3激酶的p85和p55PIK亚基，和Vav的靶分子。Tec通过其SH2结构域独立于其激酶活性与Vav相关。相反，PI-3激酶的p85和p55 PIK亚基与Tec的SH 2激酶结构域相关，依赖于Tec激酶活性。与这些一致，IL-6或IL-3诱导Tec与哺乳动物细胞中PI-3激酶的p85亚基之间的关联。这些发现表明Tec酪氨酸激酶可能通过JAK将细胞因子受体连接到PI-3激酶。
Tec/Btk tyrosine kinases are members of a subgroup of Src tyrosine kinase family. They are reported to be activated in response to cytokines, such as IL-3 and IL-6. Janus kinases (JAKs) are known to associate with certain cytokine receptors, e.g. gp130, the signal transducing subunit of IL-6 receptor, and the common β chain of IL-3 receptor, which can be activated upon receptor dimerization in response to cytokines. Here we show the association between Jak1/Jak2 and Tec or Jak1 and Btk. Furthermore, Jak1 but not Jak2 induces tyrosine phosphorylation of Btk, but not Tec. These observations suggest that upon cytokine stimulation JAKs activate Tec/Btk or induce their dimerization resulting in endogenous tyrosine phosphorylation. Furthermore using a yeast two-hybrid system we have identified the target molecules for Tec, the p85 and p55PIK subunits of PI-3 kinase, and Vav. Tec associated with Vav through its SH2 domain independently of its kinase activity. In contrast the p85 and p55PIK subunits of PI-3 kinase associated with the SH2-kinase domain of Tec, dependent on Tec kinase activity. Consistent with these, IL-6 or IL-3 induced the association between Tec and the p85 subunit of PI-3 kinase in mammalian cells. These findings suggest that Tec tyrosine kinase links cytokine receptors to PI-3 kinase probably through JAKs.