Stimulation of interferon regulatory factor-1 by prolactin.
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 NFkappaB 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.
Yu-Lee
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Department of Medicine, Cell and Molecular Biology Program, Baylor College of Medicine, Houston, Texas 77030, USA. yulee@bcm.tmc.edu
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D053613:Janus Kinase 1; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D011981:Receptors, Prolactin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1