Taga T
Institute for Molecular and Cellular Biology, Osaka University.
Nihon Rinsho. 1992 Aug;50(8):1802-10.
Functional pleiotropy and redundancy are characteristic features of cytokines. To understand the signaling mechanisms of such cytokines, we have proposed a two-chain interleukin-6 receptor (IL-6-R) model: IL-6 triggers the association of a ligand-binding chain (IL-6-R) and a non-binding signal transducer (gp130) to form a high-affinity receptor complex, causing transmission of the signal by the cytoplasmic portion of gp130. This model would explain the functional redundancy of cytokines if we were to assume that gp130 interacts with several different receptor chains. Here we present data indicating that gp130 functions as a common signal transducer for IL-6, oncostatin M (OM), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF). We show that anti-gp130 monoclonal antibodies completely block the biological responses induced by all of these factors. Since LIF functions as a cholinergic differentiation factor in nerve cells as does CNTF, these results suggest that gp130 may also play a role in the neural system.
功能多效性和冗余性是细胞因子的特征。为了解这类细胞因子的信号传导机制，我们提出了一种双链白细胞介素-6受体（IL-6-R）模型：IL-6触发配体结合链（IL-6-R）和非结合信号转导子（gp130）的缔合，形成高亲和力受体复合物，通过gp130的细胞质部分传递信号。如果我们假设gp130与几种不同的受体链相互作用，那么这个模型将解释细胞因子的功能冗余性。在此，我们展示的数据表明，gp130作为IL-6、抑瘤素M（OM）、白血病抑制因子（LIF）和睫状神经营养因子（CNTF）的共同信号转导子发挥作用。我们发现抗gp130单克隆抗体完全阻断了所有这些因子诱导的生物学反应。由于LIF与CNTF一样在神经细胞中作为胆碱能分化因子发挥作用，这些结果表明gp130可能也在神经系统中发挥作用。
