Hirano T
Department of Molecular Oncology, Osaka University Medical School, Japan.
Int Rev Immunol. 1998;16(3-4):249-84. doi: 10.3109/08830189809042997.
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.
自1986年白细胞介素6（IL-6）分子克隆成功以来，已经过去了十年。IL-6是一种典型的细胞因子，具有功能多效性和冗余性。IL-6参与免疫反应、炎症和造血过程。IL-6受体由一个IL-6结合α链和一个信号转导子gp130组成，gp130在IL-6相关细胞因子亚家族的受体中是共享的。受体亚基的共享是细胞因子受体的一个普遍特征，为细胞因子的功能冗余提供了分子基础。JAK酪氨酸激酶是一个关键分子，它可以通过诱导细胞因子受体（如IL-6情况下的gp130）的酪氨酸磷酸化来启动多条信号转导途径，在gp130上招募了几种信号分子，包括信号转导和转录激活因子STAT以及与Ras-MAP激酶途径相连的SHP-2。JAK还可以直接激活STAT和Tec等信号分子。这些多条信号转导途径密切调节包括c-myc、c-myb、junB、IRF1、egr-1和bcl-2在内的几种基因的表达，从而导致细胞生长、分化和存活的诱导。IL-6及其受体的表达失调与多种疾病有关。
