Characterization of R-ras3/m-ras null mice reveals a potential role in trophic factor signaling.
Characterization of R-ras3/m-ras null mice reveals a potential role in trophic factor signaling.
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R-ras3/m-ras 缺失小鼠的表征揭示了其在营养因子信号传导中的潜在作用。
DOI：
10.1128/mcb.00476-06
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发表时间：
2006
影响因子：
5.3
通讯作者：
Chan,AndrewM-L
中科院分区：
文献类型：
--
作者：
NunezRodriguez,Nelson;Lee,IvyNL;Banno,Asoka;Qiao,HuiF;Qiao,RuiF;Yao,Zhong;Hoang,Thuong;Kimmelman,AlecC;Chan,AndrewM-L
R-Ras 3/M-Ras是小分子量GTP结合蛋白RAS超家族的成员。先前的研究已经证明了在中枢神经系统的几个区域中的高水平表达，并且M-Ras的组成型活性形式促进细胞骨架重组、细胞转化、存活和分化。然而，M-Ras在胚胎发生和出生后发育过程中的生理功能尚未阐明。通过使用特定的M-Ras抗体，我们证明了除了神经元外，星形胶质细胞中也有高水平的M-Ras表达。内源性M-Ras被星形胶质细胞中的几种营养因子激活，包括表皮生长因子（EGF）、碱性成纤维细胞生长因子和肝细胞生长因子。有趣的是，与原型Ras相比，EGF对M-Ras的激活更持久。产生M-Ras缺陷的小鼠品系以研究其在发育中的作用。M-Ras基因敲除小鼠表现正常，没有可检测到的形态学和神经学缺陷。此外，来自Mras −/−小鼠的原代星形胶质细胞在对营养因子的反应中，丝裂原活化蛋白激酶和磷脂酰肌醇3-激酶途径的激活似乎没有显示出实质性的改变。
R-Ras3/M-Ras is a member of theRASsuperfamily of small-molecular-weight GTP-binding proteins. Previous studies have demonstrated high levels of expression in several regions of the central nervous system, and a constitutively active form of M-Ras promotes cytoskeletal reorganization, cellular transformation, survival, and differentiation. However, the physiological functions of M-Ras during embryogenesis and postnatal development have not been elucidated. By using a specific M-Ras antibody, we demonstrated a high level of M-Ras expression in astrocytes, in addition to neurons. Endogenous M-Ras was activated by several trophic factors in astrocytes, including epidermal growth factor (EGF), basic fibroblast growth factor, and hepatocyte growth factor. Interestingly, M-Ras activation by EGF was more sustained compared to prototypic Ras. A mouse strain deficient in M-Ras was generated to investigate its role in development. M-Ras null mice appeared phenotypically normal, and there was a lack of detectable morphological and neurological defects. In addition, primary astrocytes derived fromMras−/−mice did not appear to display substantial alterations in the activation of both the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways in response to trophic factors.