Nuclear Jak2 and transcription factor NF1-C2: a novel mechanism of prolactin signaling in mammary epithelial cells.
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.
Nilsson
Jeanette
J
Department of CMB/Molecular Biology, Box 462, S-405 30 Göteborg, Sweden.
Bjursell
Gunnar
G
Kannius-Janson
Marie
M
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
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