A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta

A novel, soluble homologue of the human IL-10 receptor with preferential expression in placenta
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DOI:
10.1038/sj.gene.6363786
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发表时间:
2001-10-01
期刊:
影响因子:
5
通讯作者:
Sabat, R
Sabat, R
中科院分区:
医学3区
文献类型:
--
作者:
Gruenberg, BH;Schoenemeyer, A;Sabat, R

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细胞因子受体家族2型(CRF2)包括干扰素和白介素10(IL-10)等重要免疫调节剂的受体。我们在这个家族中发现了一个新的成员,它代表了这个组中第一个完全可溶的受体,因此被命名为CRF2-s1(CRF2-s1)。CRF2-S1基因全长约28kb,位于第6号染色体上,与CRF2成员干扰素-γ受体1和IL-20受体1距离较近。它由7个外显子组成,产生两种不同的mRNA剪接变异体:CRF2-S1-Long和CRF2-S1-Short。CRF2-S1-Long和CRF2-S1-Short分别编码263和231个氨基酸。对预测的蛋白质结构的比较导致了假设,即每个受体变体与不同的配体结合。对人类mRNA表达的定量分析显示,这两种剪接形式都存在非常有限的模式。CRF2-S1是该受体家族的第一个成员,既不在静息状态下表达,也不在刺激后的白细胞中表达。CRF2-S1-Long仅在胎盘中表达,而CRF2-S1-Short在人乳腺中也有表达,在皮肤、脾、胸腺和胃中表达水平较低。CRF2-S1在胎盘中的优势表达提示了该受体在建立和维持成功妊娠中的作用。
The cytokine receptor family type 2 (CRF2) comprises receptors for important immunomediators like interferons and interleukin-10 (IL-10). We identified a novel member of this family which represents the first exclusively soluble receptor in this group and was therefore designated as CRF2-soluble 1 (CRF2-s1). The CRF2-s1 gene covers about 28 kb and is located on chromosome 6 in close proximity to the CRF2 members interferon (IFN)-gamma receptor 1 and IL-20 receptor 1. It comprises seven exons and generates two different mRNA splice variants, CRF2-s1-long and CRF2-s1-short. CRF2-s1-long and CRF2-s1-short encode proteins of 263 and 231 amino acids, respectively. A comparison of predicted protein structures led to the postulation that each receptor variants binds a different ligand. Quantitative analysis of human mRNA expression revealed a very restricted pattern for both splice forms. CRF2-s1 turned out to be the first member of this receptor family which was expressed neither in resting nor in stimulated leucocyte populations. CRF2-s1-long was only expressed in placenta, whereas CRF2-s1-short was additionally expressed in human mammary gland and, at a lower level, in skin, spleen, thymus and stomach. The preferential expression of CRF2-s1 in placenta suggests a role for this receptor in establishing and maintaining successful pregnancy.