Wang Shu-Zong, Roberts R Michael
Department of Veterinary Pathology, University of Missouri, Columbia, Missouri 65211, USA.
Endocrinology. 2004 Dec;145(12):5820-31. doi: 10.1210/en.2004-0991. Epub 2004 Sep 2.
During early pregnancy in ruminants, a type I interferon (IFN-tau) signals from the conceptus to the mother to ensure the functional survival of the corpus luteum. IFN-tau operates through binding to the type I IFN receptor (IFNR). Here we have explored the possibility that IFNAR2, one of the two subunits of the receptor, might interact with hitherto unknown signal transduction factors in the uterus that link IFN action to pathways other than the well established Janus kinase-signal transducer and activator of transcription pathways. A yeast two-hybrid screen of an ovine (ov) endometrial cDNA library with the carboxyl-terminal 185 amino acids of ovIFNAR2 as bait identified stress-activated protein kinase-interacting protein 1 (ovSin1) as a protein that bound constitutively through its own carboxyl terminus to the receptor. ovSin1 is a little studied, 522-amino acid-long polypeptide (molecular weight, 59,200) that is highly conserved across vertebrates, but has identifiable orthologs in Drosophila and yeast. It appears to be expressed ubiquitously in mammals, although in low abundance, in a wide range of mammalian tissues in addition to endometrium. Sin1 mRNA occurs in at least two alternatively spliced forms, the smaller of which lacks a 108-bp internal exon. ovSin1, although not exhibiting features of a membrane-spanning protein, such as IFNAR2, is concentrated predominantly in luminal and glandular epithelial cells of the uterine endometrium. When ovSin1 and ovIFNAR2 are coexpressed, the two proteins can be coimmunoprecipitated and colocalized to the plasma membrane and to perinuclear structures. Sin1 provides a possible link among type I IFN action, stress-activated signaling pathways, and control of prostaglandin production.
在反刍动物的妊娠早期，一种I型干扰素（IFN-τ）从孕体向母体发出信号，以确保黄体的功能存活。IFN-τ通过与I型干扰素受体（IFNR）结合发挥作用。在此，我们探讨了受体的两个亚基之一IFNAR2可能与子宫中迄今未知的信号转导因子相互作用的可能性，这些因子将IFN的作用与已确立的Janus激酶-信号转导子和转录激活子途径以外的途径联系起来。以ovIFNAR2的羧基末端185个氨基酸为诱饵，对绵羊（ov）子宫内膜cDNA文库进行酵母双杂交筛选，确定应激激活蛋白激酶相互作用蛋白1（ovSin1）是一种通过其自身羧基末端与受体组成性结合的蛋白质。ovSin1是一种研究较少的522个氨基酸长的多肽（分子量59200），在脊椎动物中高度保守，但在果蝇和酵母中具有可识别的直系同源物。它似乎在哺乳动物中广泛表达，尽管丰度较低，除了子宫内膜外，还存在于多种哺乳动物组织中。Sin1 mRNA至少以两种可变剪接形式出现，其中较小的一种缺少一个108 bp的内部外显子。ovSin1虽然不具有跨膜蛋白（如IFNAR2）的特征，但主要集中在子宫内膜的腔上皮细胞和腺上皮细胞中。当ovSin1和ovIFNAR2共表达时，这两种蛋白质可以被共免疫沉淀，并共定位于质膜和核周结构。Sin1可能在I型干扰素作用、应激激活信号通路和前列腺素产生的控制之间提供了一种联系。
