Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse cellular functions including proliferation, differentiation, angiogenesis and protection against apoptosis and inflammation. To understand the mechanism of PRL signaling in T cells, we have cloned both PRL and its receptor (PRL-R), one potent mediator of PRL signaling, Stat5b, and a panel of PRL-inducible immediate early genes from T cells. We are employing these genes as tools with which to understand how PRL regulates the expression of one target gene, the transcription factor interferon regulatory factor-1 (IRF-1), which is a multifunctional immune regulator gene. In investigating regulatory events along the PRL-R/JAK/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross-talk between Stat and NFkB signaling pathways also regulates IRF-1 promoter activity. These findings have much broader implications not only for T lymphocytes but also for other PRL responsive target cells and tissues.
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