Activation of Fes tyrosine kinase by gp130, an interleukin-6 family cytokine signal transducer, and their association
Activation of Fes tyrosine kinase by gp130, an interleukin-6 family cytokine signal transducer, and their association
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gp130（一种白细胞介素 6 家族细胞因子信号转导器）对 Fes 酪氨酸激酶的激活及其关联
DOI：
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发表时间：
1995
影响因子：
4.8
通讯作者：
Toshio Hirano
中科院分区：
文献类型：
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作者：
Tadashi Matsuda;Toshiyuki Fukada;M. Takahashi;Yoshiki Okuyama;Yoshio Fujitani;Y. Hanazono;H. Hirai;Toshio Hirano
Gp130是白介素6(IL-6)相关细胞因子亚家族受体的信号转导亚单位，包括IL-6、白血病抑制因子、抑瘤素M、IL-11和睫状神经营养因子，提示gp130介导的信号参与免疫反应、造血、炎症、内分泌和神经系统活动。我们以前发现gp130刺激可以迅速激活Jak、BTK和Tec酪氨酸激酶，所有这些都与gp130密切相关。为了进一步阐明通过gp130的细胞内信号转导，我们研究了另一种非受体酪氨酸激酶p92c-fes(Fes)的可能参与。我们发现gp130刺激能迅速诱导FES的酪氨酸磷酸化，并激活其在造血祖细胞中的激酶活性。此外，Fes与gp130的关联不依赖于配体刺激，如Jak、BTK和Tec酪氨酸激酶。这些结果表明，多个非受体酪氨酸激酶参与了gp130介导的信号转导通路。由于gp130和Fes不仅在造血系细胞中表达，而且在心脏和神经细胞中也有表达，Fes可能通过gp130在这些组织中发挥信号转导作用。
gp130 is a signal-transducing subunit of receptors for the interleukin- 6 (IL-6)-related cytokine subfamily including IL-6, leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor, indicating that gp130-mediated signals are involved in the immune response, hematopoiesis, inflammation, and endocrine and nervous system activity. We previously showed that gp130 stimulation rapidly activates Jak, Btk, and Tec tyrosine kinases, all of which constitutively associate with gp130. To further elucidate intracellular signal transduction through gp130, we examined the possible involvement of another nonreceptor tyrosine kinase, p92c-fes (Fes). We showed that gp130 stimulation rapidly induced tyrosine phosphorylation of Fes and actually activated its kinase activity in hematopoietic lineage cells. Furthermore, Fes associated with gp130 independently of ligand stimulation like Jak, Btk, and Tec tyrosine kinases. These results indicate that multiple nonreceptor tyrosine kinases are involved in the gp130-mediated signal transduction pathway. Because both gp130 and Fes are expressed not only in hematopoietic lineage cells but also in heart and nerve cells, Fes may play a role in signal transduction through gp130 in these tissues.