A novel mesoderm inducer, Madr2 functions in the activin signal transduction pathway
A novel mesoderm inducer, Madr2 functions in the activin signal transduction pathway
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DOI：
10.1101/gad.10.15.1880
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发表时间：
1996-08-01
影响因子：
10.5
通讯作者：
Harland, RM
中科院分区：
文献类型：
--
作者：
Baker, JC;Harland, RM
克隆小鼠中胚层诱导剂的功能实验已经确定了小鼠基因Mad Related 2(Madr2)。MADR2可以从非洲爪哇外胚层诱导出背侧中胚层，并可以模仿组织者将相邻细胞招募到第二轴。通过分析LacZ/MADR2融合蛋白的表达，我们发现MADR2定位于第二轴的深层前部细胞的细胞核中，而在表皮和更多的后部细胞中，该蛋白定位于细胞质。这种上下文相关的核定位表明，在胚胎的某些区域，Madr2对定位信号做出反应，并放大该信号以形成第二轴。此外，虽然外胚层外植体中MADR2仍未定位，但激活素的加入增加了MADR2在细胞核中的浓度。值得注意的是，即使在没有激活素的情况下，与Madr2羧基末端的功能性LacZ融合也是核定位的。这表明Madr2含有一个激活下游成分的结构域和一个将蛋白质锚定在细胞质中的抑制性结构域。激活素对MADR2的核定位以及过表达诱导的激活素样表型表明，MADR2是介导激活素活性的信号转导成分。
A functional assay to clone mouse mesoderm inducers has identified the mouse gene Mad related 2 (Madr2). Madr2 induces dorsal mesoderm from Xenopus ectoderm and can mimic the organizer in recruiting neighboring cells into a second axis. By analyzing the expression of a lacZ/Madr2 fusion protein, we find Madr2 confined to the nucleus in the deep, anterior cells of the second axis, whereas in epidermal and more posterior cells the protein is cytoplasmically localized. This context-dependent nuclear localization suggests that in certain regions of the embryo, Madr2 responds to a localized signal and amplifies this signal to farm the second axis. furthermore, although Madr2 remains unlocalized in ectodermal explants, addition of activin enhances the concentration of Madr2 in the nucleus. Significantly, a functional lacZ fusion to a carboxy-terminal portion of Madr2 is nuclear localized even in the absence of activin. This indicates that Madr2 contains a domain that fan activate downstream components and a repressive domain that anchors the protein in the cytoplasm. Nuclear localization of Madr2 in response to activin, and the activin-like phenotypes induced by overexpression of Madr2 indicate that Madr2 is a signal transduction component that mediates the activity of activin.