http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Effects of interferon-[] on activation of the Jak/Stat signal transduction pathway and regulation of ovine endometrial gene expression
Interferon-[] (IFN[]) is a Type I IFN produced by the trophectoderm of ruminant conceptuses for maternal recognition of pregnancy. IFN[] prevents transcriptional up-regulation of estrogen receptor α (ERα) and oxytocin receptor (OTR) genes in the endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) and simultaneously stimulates expression of many IFN-stimulated genes (ISGs) in the stroma and deep glandular epithelium (dGE). However, the cellular and molecular mechanisms by which IFN[] elicits positive and negative effects on gene expression in the endometrium are largely unknown. Therefore, the objective of this study was to determine the signal transduction pathway activated by IFN[] and how it functions to regulate ISG expression. IFN[] induced persistent tyrosine phosphorylation and nuclear translocation of Stats 1 and 2 in ovine LE cells. However, Stats 3, 5a/b and 6 were transiently activated and did not bind DNA. IFN[] elicited formation of IFN-stimulated gene factor 3 (ISGF3), a heterotrimer consisting of Stat1, Stat2 and IRF-9, which persistently activated transcription. IFN[] also induced formation of γ-activated factor (GAF), a homodimer of Stat1, which initially activated, but then suppressed transcription of certain target genes. In fibroblast cell lines, IFN[] stimulated expression of Stat1, Stat2, IFN-regulatory factor (IRF)-9, 40/46-kDa 2', 5'-oligoadenylate synthetase (OAS) and 69/71-kDa OAS through ISGF3. In contrast, IFN[] stimulated IRF-1 and 100-kDa OAS expression through GAF. IFN[] signaled effectively through Stat1α, Stat1β or a mutant Stat1α that cannot be serine phosphorylated. However, mutation of the tyrosine phosphorylation site or src-homology 2 (SH2) domain on Stat1 attenuated signal transduction. Collectively, these results indicate critical roles for Stat1, Stat2 and IRF-9 in the positive effects of IFN[] on ISG transcription within the ovine endometrium.
"Major subject: Physiology of Reproduction".
Issued also on microfiche from Lange Micrographics.
Includes bibliographical references (leaves 118-148).