Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.
Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.
复制标题
哺乳动物矮鳍鱼响应转化生长因子β而被磷酸化，并参与细胞生长的控制。
DOI：
10.1073/pnas.93.17.8940
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发表时间：
1996
影响因子：
11.1
通讯作者：
Wang,XF
中科院分区：
文献类型：
--
作者：
Yingling,JM;Das,P;Savage,C;Zhang,M;Padgett,RW;Wang,XF
在果蝇和秀丽隐杆线虫中，侏儒蛋白家族在遗传上与转化生长因子β（TGF-β）样信号通路有关。为了研究这些蛋白在哺乳动物信号通路中的作用，我们分离并研究了两种小鼠侏儒蛋白，侏儒蛋白-A和侏儒蛋白-C。使用针对侏儒蛋白-A和侏儒蛋白-C的抗体，我们表明，这两个侏儒蛋白和免疫原性相关的蛋白质，大概也是侏儒蛋白，磷酸化的时间和剂量依赖性的方式响应TGF-β。骨形态发生蛋白2，一种TGF-β超家族配体，仅诱导相关侏儒蛋白的磷酸化。因此，TGF-β超家族成员可能使用重叠但不同的侏儒蛋白来介导它们的细胞内信号。此外，无论是侏儒蛋白-A或侏儒蛋白-C的瞬时过表达导致生长停滞，牵连的侏儒在生长调节。这项工作提供了强有力的生物化学和初步的功能证据表明，dwarfin-A和dwarfin-C代表了哺乳动物蛋白家族的原型成员，这些蛋白可能作为TGF-β超家族成员信号通路的介体。
The dwarfin protein family has been genetically implicated in transforming growth factor beta (TGF-beta)-like signaling pathways in Drosophila and Caenorhabditis elegans. To investigate the role of these proteins in mammalian signaling pathways, we have isolated and studied two murine dwarfins, dwarfin-A and dwarfin-C. Using antibodies against dwarfin-A and dwarfin-C, we show that these two dwarfins and an immunogenically related protein, presumably also a dwarfin, are phosphorylated in a time- and dose-dependent manner in response to TGF-beta. Bone morphogenetic protein 2, a TGF-beta superfamily ligand, induces phosphorylation of only the related dwarfin protein. Thus, TGF-beta superfamily members may use overlapping yet distinct dwarfins to mediate their intracellular signals. Furthermore, transient overexpression of either dwarfin-A or dwarfin-C causes growth arrest, implicating the dwarfins in growth regulation. This work provides strong biochemical and preliminary functional evidence that dwarfin-A and dwarfin-C represent prototypic members of a family of mammalian proteins that may serve as mediators of signaling pathways for TGF-beta superfamily members.