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首页> 外文期刊>Molecular and Cellular Biology >Activation of H-Ras in the Endoplasmic Reticulum by the RasGRF Family Guanine Nucleotide Exchange Factors
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Activation of H-Ras in the Endoplasmic Reticulum by the RasGRF Family Guanine Nucleotide Exchange Factors

机译：RasGRF家族鸟嘌呤核苷酸交换因子激活内质网中的H-Ras。

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摘要

Recent findings indicate that in addition to its location in the peripheral plasma membrane, H-Ras is found in endomembranes like the endoplasmic reticulum and the Golgi complex. In these locations H-Ras is functional and can efficiently engage downstream effectors, but little is known about how its activation is regulated in these environments. Here we show that the RasGRF family exchange factors, both endogenous and ectopically expressed, are present in the endoplasmic reticulum but not in the Golgi complex. With the aid of H-Ras constructs specifically tethered to the plasma membrane, endoplasmic reticulum, and Golgi complex, we demonstrate that RasGRF1 and RasGRF2 can activate plasma membrane and reticular, but not Golgi-associated, H-Ras. We also show that RasGRF DH domain is required for the activation of H-Ras in the endoplasmic reticulum but not in the plasma membrane. Furthermore, we demonstrate that RasGRF mediation favors the activation of reticular H-Ras by lysophosphatidic acid treatment whereas plasma membrane H-Ras is made more responsive to stimulation by ionomycin. Overall, our results provide the initial insights into the regulation of H-Ras activation in the endoplasmic reticulum.
机译：最近的发现表明，除了其在外周质膜中的位置外，还在内膜如内质网和高尔基体中发现了H-Ras。在这些位置，H-Ras起作用并且可以有效地与下游效应子接合，但对于在这些环境中如何调节其激活知之甚少。在这里，我们显示内质网和异位表达的RasGRF家族交换因子都存在于内质网中，而不存在于高尔基体中。借助专门拴在质膜，内质网和高尔基体上的H-Ras构建体，我们证明RasGRF1和RasGRF2可以激活质膜和网状细胞，但不能激活高尔基体相关的H-Ras。我们还显示RasGRF DH域是激活内质网而非质膜中H-Ras所必需的。此外，我们证明了RasGRF介导通过溶血磷脂酸处理促进网状H-Ras的激活，而质膜H-Ras对离子霉素的刺激反应更敏感。总体而言，我们的研究结果为内质网中H-Ras激活的调控提供了初步见识。

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