Sugamura K
Department of Bacteriology, Tohoku University School of Medicine, Sendai, Japan.
Hum Cell. 1994 Mar;7(1):1-5.
IL-2 regulates growth and differentiation of various types of cells in the immune system via its interaction with IL-2 receptor (IL-2R). The high and intermediate-affinity IL-2Rs, which consist of the alpha beta gamma heterotrimer complex and the beta gamma heterodimer complex, respectively, harbor the function of the intracellular signal transduction, indicating that the beta and gamma chains are indispensable for the signal transduction but not the alpha chain. The reconstitution studies of IL-2Rs with alpha, beta and gamma chain genes demonstrated that each subunit has potential for altering the affinity of the receptor, and the cytoplasmic domains of the beta and gamma chains participate in signal transduction in terms of cell growth, activation of alpha tyrosine kinase and enhancement of c-myc, c-fos and c-jun transcription. The region containing the SH2 homologous sequence of the gamma chain should have a critical function for signal transduction. On the other hand, common subunits are known to be shared among receptors for IL-3, IL-5 and GM-CSF, and receptors for IL-6, LIF, OSM and LIF. We have demonstrated that the monoclonal antibody specific for the IL-2R gamma chain completely inhibited not only IL-2-dependent cell growth but also IL-4-dependent, IL-7-dependent, and IL-9-dependent cell growth, suggesting that the gamma chain is possibly shared among receptors for IL-2, IL-4, IL-7 and IL-9. Impairment of the gamma chain function is considered to be closely related to human XSCID characterized by profound T cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)
白细胞介素-2(IL-2)通过与白细胞介素-2受体(IL-2R)相互作用来调节免疫系统中各类细胞的生长和分化。高亲和力和中等亲和力的IL-2R,分别由αβγ异源三聚体复合物和βγ异源二聚体复合物组成,具有细胞内信号转导功能,这表明β链和γ链对于信号转导是不可或缺的,而α链并非如此。用α、β和γ链基因对IL-2R进行的重组研究表明,每个亚基都有改变受体亲和力的潜力,并且β链和γ链的胞质结构域在细胞生长、α酪氨酸激酶激活以及c-myc、c-fos和c-jun转录增强方面参与信号转导。γ链中包含SH2同源序列的区域对信号转导应具有关键作用。另一方面,已知IL-3、IL-5和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的受体以及IL-6、白血病抑制因子(LIF)、抑瘤素M(OSM)和睫状神经营养因子(CNTF)的受体之间存在共同亚基。我们已经证明,针对IL-2Rγ链的单克隆抗体不仅能完全抑制依赖IL-2的细胞生长,还能抑制依赖IL-4、IL-7和IL-9的细胞生长,这表明γ链可能在IL-2、IL-4、IL-7和IL-9的受体之间共享。γ链功能受损被认为与以严重T细胞缺陷为特征的人类X连锁重症联合免疫缺陷病(XSCID)密切相关。(摘要截短于250字)