Nilsson Jeanette, Bjursell Gunnar, Kannius-Janson Marie
Department of CMB/Molecular Biology, Box 462, S-405 30 Göteborg, Sweden.
Mol Cell Biol. 2006 Aug;26(15):5663-74. doi: 10.1128/MCB.02095-05.
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.
催乳素在乳腺上皮细胞中转导信号的经典机制是通过质膜相关的催乳素受体- Janus激酶2（Jak2）复合物激活细胞溶质信号转导子和转录激活子5（Stat5）。在此，我们描述了一条替代途径，催乳素通过定位于细胞核的Jak2激活转录因子核因子1-C2（NF1-C2）。先前的报道已证明Jak2存在核定位，但核Jak2的生理重要性尚不清楚。我们证明核Jak2通过酪氨酸磷酸化和蛋白酶体降解来调节活性NF1-C2的量。我们的数据还证明了催乳素与p53以及通过核Jak2和NF1-C2的乳基因羧基酯脂肪酶之间的联系。因此，我们描述了一种新的途径，通过该途径核Jak2在乳腺上皮细胞中受到催乳素的调节。
