Matsuda T, Takahashi-Tezuka M, Fukada T, Okuyama Y, Fujitani Y, Tsukada S, Mano H, Hirai H, Witte O N, Hirano T
Division of Molecular Oncology, Osaka University Medical School, Japan.
Blood. 1995 Feb 1;85(3):627-33.
Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, although the cytoplasmic region of gp130 does not contain any catalytic domain. In this study we show that in addition to Jak family tyrosine kinase, the stimulation of gp130 by IL-6 plus soluble IL-6 receptor alpha induced the activation of Btk and Tec tyrosine kinases, whereas IL-3 and granulocyte colony-stimulating factor activated Tec but not Btk in a pro-B cell line. Furthermore, both Btk and Tec kinases were associated with gp130 without the ligand stimulation. Because Btk is a critical tyrosine kinase for B lymphopoiesis and Tec is considered to be involved in hematopoiesis, the results suggest the involvement of gp130-Btk-Tec signal pathway in early lymphohematopoiesis.
白细胞介素-6（IL-6）、白血病抑制因子、抑瘤素M、IL-11和睫状神经营养因子构成了细胞因子的IL-6家族，在造血、免疫反应和神经系统中发挥重要作用。IL-6家族细胞因子的受体共享gp130，信号通过gp130产生，尽管gp130的胞质区域不包含任何催化结构域。在本研究中，我们发现，除了Jak家族酪氨酸激酶外，IL-6加可溶性IL-6受体α对gp130的刺激还诱导了Btk和Tec酪氨酸激酶的激活，而在一个前B细胞系中，IL-3和粒细胞集落刺激因子激活了Tec，但未激活Btk。此外，在没有配体刺激的情况下，Btk和Tec激酶都与gp130相关联。由于Btk是B淋巴细胞生成的关键酪氨酸激酶，且Tec被认为参与造血过程，因此结果表明gp130-Btk-Tec信号通路参与早期淋巴细胞生成。
