Interleukin 6 and its receptor: ten years later.
Interleukin 6 and its receptor: ten years later.
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DOI：
10.3109/08830189809042997
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发表时间：
1998
影响因子：
5
通讯作者：
T. Hirano
中科院分区：
文献类型：
--
作者：
T. Hirano
自1986年白细胞介素6（IL-6）的分子克隆以来，已经过去了10年。IL-6是一种典型的细胞因子，具有功能多效性和冗余性。IL-6参与免疫应答、炎症和造血。IL-6受体由IL-6结合α链和信号转导子gp 130组成，其在IL-6相关细胞因子亚家族的受体中共享。受体亚基的共享是细胞因子受体的一般特征，并为细胞因子的功能冗余提供了分子基础。JAK酪氨酸激酶是通过诱导细胞因子受体（在IL-6的情况下为gp 130）的酪氨酸磷酸化来启动多种信号转导途径的关键分子，在gp 130上募集若干信号传导分子，包括STAT（信号转导子和转录激活子）和SHP-2（其连接到Ras-MAP激酶途径）。JAK还可以直接激活信号分子，如STAT和Tec。这些多个信号转导通路密切调节包括c-myc、c-myb、junB、IRF 1、bcl-1和bcl-2在内的几种基因的表达，从而诱导细胞生长、分化和存活。IL-6及其受体的表达失调与多种疾病有关。
Ten years have passed since the molecular cloning of interleukin 6 (IL-6) in 1986. IL-6 is a typical cytokine, exhibiting functional pleiotropy and redundancy. IL-6 is involved in the immune response, inflammation, and hematopoiesis. The IL-6 receptor consists of an IL-6 binding alpha chain and a signal transducer, gp130, which is shared among the receptors for the IL-6 related cytokine subfamily. The sharing of a receptor subunit is a general feature of cytokine receptors and provides the molecular basis for the functional redundancy of cytokines. JAK tyrosine kinase is a key molecule that can initiate multiple signal-transduction pathways by inducing the tyrosine-phosphorylation of the cytokine receptor, gp130 in the case of IL-6, on which several signaling molecules are recruited, including STAT, a signal transducer and activator of transcription, and SHP-2, which links to the Ras-MAP kinase pathway. JAK can also directly activate signaling molecules such as STAT and Tec. These multiple signal-transduction pathways intimately regulate the expression of several genes including c-myc, c-myb, junB, IRF1, egr-1, and bcl-2, leading to the induction of cell growth, differentiation, and survival. The deregulated expression of IL-6 and its receptor is involved in a variety of diseases.