title: Nuclear Jak2 and transcription factor NF1-C2: a novel mechanism of prolactin signaling in mammary epithelial cells.
abstract: The classical mechanism by which prolactin transduces its signal in mammary epithelial cells is by activation of cytosolic signal transducer and activator of transcription 5 (Stat5) via a plasma membrane-associated prolactin receptor-Janus kinase 2 (Jak2) complex. Here we describe an alternative pathway through which prolactin via Jak2 localized in the nucleus activates the transcription factor nuclear factor 1-C2 (NF1-C2). Previous reports have demonstrated a nuclear localization of Jak2, but the physiologic importance of nuclear Jak2 has not been clear. We demonstrate that nuclear Jak2 regulates the amount of active NF1-C2 through tyrosine phosphorylation and proteasomal degradation. Our data also demonstrate a link between prolactin and p53 as well as the milk gene carboxyl ester lipase through nuclear Jak2 and NF1-C2. Hence, we describe a novel pathway through which nuclear Jak2 is subject to regulation by prolactin in mammary epithelial cells.
authors.affiliation: Department of CMB/Molecular Biology, Box 462, S-405 30 Göteborg, Sweden.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Nilsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Bjursell
authors.forename: Marie
authors.initials: M
authors.lastname: Kannius-Janson
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D042361:Mammary Glands, Human / Q000033:anatomy & histology* / Q000378:metabolism; D051379:Mice; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism
chemical_list: D051839:NFI Transcription Factors; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D014443:Tyrosine; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; C054621:CEL protein, human; D008049:Lipase; D046988:Proteasome Endopeptidase Complex