Lai C F, Ripperger J, Morella K K, Jurlander J, Hawley T S, Carson W E, Kordula T, Caligiuri M A, Hawley R G, Fey G H, Baumann H
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
J Biol Chem. 1996 Jun 14;271(24):13968-75. doi: 10.1074/jbc.271.24.13968.
The cytoplasmic domain of the receptor for interleukin 10 (IL-10R) contains two box 3 sequence motifs that have been identified in the signal-transducing receptor subunits for IL-6-type cytokines and noted to be required for activating STAT3 and inducing transcription through IL-6-responsive elements. To determine whether the IL-10R has signaling functions similar to IL-6R in cells normally expressing these receptors, leukocytes of the B-, T-, and NK-cell lineages were treated with either cytokine. Both cytokines activated factors that bound to the sis-inducible element and included STAT1 and STAT3. The cell response to IL-10 characteristically differed from that to IL-2/IL-15, IL-4, and interferon gamma. The signaling capabilities of the IL-10R for activating specific STAT proteins and inducing gene transcription were defined by reconstitution of receptor functions in transfected tissue culture cells. COS-1 cells, co-expressing the human IL-10R and individual STAT proteins, confirmed a preference of the IL-10R for STAT3 and STAT1. Unlike many hematopoietin receptors, the IL-10R did not detectably activate STAT5. The IL-10R, together with reporter gene constructs containing different IL-6-responsive gene elements, reconstituted in hepatoma cells an induction of transcription by IL-10 that was comparable to that by IL-6. This regulation could not be appreciably modified by enhanced expression of STAT proteins. The similar actions of IL-10R and IL-6R on the induction of endogenous IL-6-responsive genes were demonstrated in hepatoma cells stably expressing the IL-10R. These receptor functions required the presence of the box 3 motifs, as shown by the analysis of the mouse IL-10R constructs containing progressively truncated cytoplasmic domains. The data demonstrate that the IL-10R, unlike other members of the interferon receptor family, is highly effective in recruiting the signaling pathways of IL-6-type cytokine receptors.
白细胞介素10受体（IL-10R）的胞质结构域包含两个box 3序列基序，这些基序已在IL-6型细胞因子的信号转导受体亚基中被鉴定出来，并被认为是激活STAT3以及通过IL-6反应元件诱导转录所必需的。为了确定在正常表达这些受体的细胞中IL-10R是否具有与IL-6R相似的信号传导功能，用这两种细胞因子分别处理B细胞、T细胞和NK细胞系的白细胞。两种细胞因子均激活了与sis诱导元件结合的因子，其中包括STAT1和STAT3。细胞对IL-10的反应在特征上不同于对IL-2/IL-15、IL-4和干扰素γ的反应。通过在转染的组织培养细胞中重建受体功能，确定了IL-10R激活特定STAT蛋白和诱导基因转录的信号传导能力。共表达人IL-10R和单个STAT蛋白的COS-1细胞证实，IL-10R优先作用于STAT3和STAT1。与许多造血因子受体不同，IL-10R未检测到可激活STAT5。IL-10R与含有不同IL-6反应基因元件的报告基因构建体一起，在肝癌细胞中重建了IL-10诱导的转录，其与IL-6诱导的转录相当。这种调节不会因STAT蛋白表达增强而明显改变。在稳定表达IL-10R的肝癌细胞中证明了IL-10R和IL-6R对内源性IL-6反应基因诱导的类似作用。如对含有逐渐截短的胞质结构域的小鼠IL-10R构建体的分析所示，这些受体功能需要box 3基序。数据表明，与干扰素受体家族的其他成员不同，IL-10R在募集IL-6型细胞因子受体的信号传导途径方面非常有效。
