IL-6-INDUCED HOMODIMERIZATION OF GP-130 AND ASSOCIATED ACTIVATION OF A TYROSINE KINASE
IL-6-INDUCED HOMODIMERIZATION OF GP-130 AND ASSOCIATED ACTIVATION OF A TYROSINE KINASE
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DOI：
10.1126/science.8511589
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发表时间：
1993-06-18
期刊：
影响因子：
56.9
通讯作者：
KISHIMOTO, T
中科院分区：
文献类型：
--
作者：
MURAKAMI, M;HIBI, M;KISHIMOTO, T
白细胞介素-6 （IL-6）的生物学功能是通过IL-6受体的信号转导组分gp130介导的，gp130与配体占据的IL-6受体（IL-6R）蛋白相关。IL-6与IL-6R的结合诱导gp130的二硫键同二聚化。酪氨酸激酶活性与二聚体gp130蛋白有关，而与单体gp130蛋白无关。用丝氨酸取代细胞质基序中的脯氨酸残基656和658，可以消除酪氨酸激酶的激活和细胞反应，但不会消除gp130的同二聚化。il -6诱导的gp130同型二聚体在功能上似乎与白血病抑制因子（LIF）受体（LIFR）和gp130响应LIF或纤毛神经营养因子（CNTF）而形成的异源二聚体相似。因此，il -6相关细胞因子信号转导的第一步可能是信号转导分子的二聚化和相关酪氨酸激酶的激活。
The biological functions of interleukin-6 (IL-6) are mediated through a signal-transducing component of the IL-6 receptor, gp130, which is associated with the ligand-occupied IL-6 receptor (IL-6R) protein. Binding of IL-6 to IL-6R induced disulfide-linked homodimerization of gp130. Tyrosine kinase activity was associated with dimerized but not monomeric gp130 protein. Substitution of serine for proline residues 656 and 658 in the cytoplasmic motif abolished tyrosine kinase activation and cellular responses but not homodimerization of gp130. The IL-6-induced gp130 homodimer appears to be similar in function to the heterodimer formed between the leukemia inhibitory factor (LIF) receptor (LIFR) and gp130 in response to the LIF or ciliary neurotrophic factor (CNTF). Thus, a general first step in IL-6-related cytokine signaling may be the dimerization of signal-transducing molecules and activation of associated tyrosine kinases.