Han C S, Mathialagan N, Klemann S W, Roberts R M
Department of Biochemistry, University of Missouri, Columbia 65211, USA.
Endocrinology. 1997 Nov;138(11):4757-67. doi: 10.1210/endo.138.11.5530.
Interferon-tau (IFN-tau), a type I IFN structurally related to IFN-alpha, is regarded as the major antiluteolytic factor secreted by the conceptus of ruminant ungulate species before definitive trophoblast attachment and implantation. It mediates its effects by acting on the uterine endometrium, where it blunts the normal pulsatile production of PGF2alpha, presumably as a result of its binding to type I IFN receptors. In this study, we describe the complementary DNAs for the two known subunits, IFNAR1 and IFNAR2, of this receptor isolated from bovine and ovine endometrial complementary DNA libraries by homology cloning. Although there is extensive inferred amino acid sequence similarity between bovine and ovine IFNAR1 (92% identity) and between bovine and ovine IFNAR2 (88% identity), they have diverged extensively from the human receptor subunits (approximately 67% and approximately 58% identity, respectively). Despite these differences in primary structure, the respective subunits from all three species are organized similarly in their extracellular and cytoplasmic regions, and the bovine and ovine subunits have each retained a number of polypeptide motifs implicated in signal transduction. These uterine receptors also appear not to be splice variants. The cloned ovine IFNAR1 subunit, for example, possesses the expected four extracellular SD100 domains of full-length bovine and huIFNAR1, and only the homologs of the so-called long form (huIFNAR2c) of human IFNAR2 have so far been identified. RT-PCR procedures indicate that the messenger RNA for both subunits are found, not only in endometrium, but in all other tissues examined except those ofpreimplantation conceptuses, which presumably cannot respond to the IFN-tau they produce. Quantitative RNase protection assays of ovine endometrial RNA show that the expression of neither subunit changes greatly during the estrous cycle or pregnancy. These data suggest that the type I IFN receptor, which is expressed by the endometrium and binds IFN-tau, is probably not a structurally unusual form.
干扰素 - τ（IFN - τ）是一种与IFN - α在结构上相关的I型干扰素，被认为是反刍有蹄类动物在滋养层最终附着和植入之前，由孕体分泌的主要抗溶黄体因子。它通过作用于子宫内膜来介导其效应，在子宫内膜中，它抑制PGF2α正常的脉冲式分泌，这可能是由于它与I型干扰素受体结合的结果。在本研究中，我们描述了通过同源克隆从牛和羊的子宫内膜互补DNA文库中分离出的该受体两个已知亚基IFNAR1和IFNAR2的互补DNA。虽然牛和羊的IFNAR1之间有广泛的推测氨基酸序列相似性（92%同一性），牛和羊的IFNAR2之间也有广泛的推测氨基酸序列相似性（88%同一性），但它们与人类受体亚基有很大差异（分别约为67%和约58%同一性）。尽管在一级结构上存在这些差异，但来自所有三个物种的各自亚基在其细胞外和细胞质区域的组织方式相似，并且牛和羊的亚基各自保留了许多与信号转导有关的多肽基序。这些子宫受体似乎也不是剪接变体。例如，克隆的羊IFNAR1亚基具有全长牛和人IFNAR1预期的四个细胞外SD100结构域，并且到目前为止仅鉴定出人类IFNAR‘2所谓长形式（huIFNAR2c）的同源物。逆转录 - 聚合酶链反应（RT-PCR）程序表明，这两个亚基的信使RNA不仅存在于子宫内膜中，还存在于除植入前孕体组织外的所有其他检测组织中，植入前孕体组织大概无法对它们产生 的IFN - τ作出反应。对羊子宫内膜RNA进行的定量核糖核酸酶保护分析表明，在发情周期或怀孕期间，这两个亚基的表达都没有太大变化。这些数据表明，由子宫内膜表达并结合IFN - τ的I型干扰素受体可能不是一种结构异常的形式。
