Groner B, Gouilleux F
Tumor Biology Center, Freiburg, Germany.
Curr Opin Genet Dev. 1995 Oct;5(5):587-94. doi: 10.1016/0959-437x(95)80027-1.
Mammary epithelial cells grow and develop with the onset of sexual maturity. In addition, lobular alveolar structures are formed during pregnancy, and quiescent differentiated cells secrete high levels of milk proteins after parturition. These events are governed by multiple hormones and growth factors and involve the sequential and synergistic action of functionally distinct signal transduction pathways. Milk protein genes have been analyzed and composite response elements have been identified in the promoter sequences. Transcription factors, which relay the hormonal signals, bind to these sequences. The factor that confers prolactin simulation to milk protein gene transcription has recently been identified. MGF/Stat5 is a latent transcription factor that becomes activated by a tyrosine-specific protein kinase, Jak2, associated with the prolactin receptor. Tyrosine phosphorylation converts the latent factor into one with DNA-binding and transcriptional activation potential. The regulation of MGF/Stat5 in vitro and in vivo indicates that it is a central component of the lactogenic hormone signaling pathway. Involvement of MGF/Stat5 in the signaling by other cytokines indicates that the same factor might be involved in regulation of growth-promoting genes, primarily in hematopoietic cells.
乳腺上皮细胞随着性成熟的开始而生长发育。此外，小叶腺泡结构在孕期形成，静止的分化细胞在分娩后分泌高水平的乳蛋白。这些事件受多种激素和生长因子调控，涉及功能不同的信号转导通路的顺序和协同作用。乳蛋白基因已被分析，并且在启动子序列中已鉴定出复合反应元件。传递激素信号的转录因子与这些序列结合。最近已鉴定出赋予催乳素对乳蛋白基因转录模拟作用的因子。MGF/Stat5是一种潜在的转录因子，它被与催乳素受体相关的酪氨酸特异性蛋白激酶Jak2激活。酪氨酸磷酸化将潜在因子转化为具有DNA结合和转录激活潜能的因子。MGF/Stat5在体外和体内的调控表明它是催乳激素信号通路的核心组成部分。MGF/Stat5参与其他细胞因子的信号传导表明同一因子可能主要参与造血细胞中促进生长基因的调控。
