ARF GTPases and their GEFs and GAPs: concepts and challenges
ARF GTPases and their GEFs and GAPs: concepts and challenges
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DOI：
10.1091/mbc.e18-12-0820
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发表时间：
2019-05-15
影响因子：
3.3
通讯作者：
Kahn，Richard A.
中科院分区：
文献类型：
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作者：
Sztul，Elizabeth;Chen，Pei-Wen;Kahn，Richard A.
需要对任何基因/蛋白质进行详细的结构、生物化学、细胞生物学和遗传学研究，以开发其在细胞中作用的模型。研究一个蛋白质家族的聚集产生额外的信息，因为可以包括分析它们的共同进化，功能的获得或丧失，结构柔韧性，以及分子机制中共享或变异的出现。通过评估功能相关的蛋白质家族，可以更深入地了解细胞生物学。在这篇综述中，我们总结了三个蛋白质家族：ARF GTP酶，激活它们的鸟嘌呤核苷酸交换因子（ARF GEFs），以及具有传播和终止信号的能力的GTP酶激活蛋白（ARF GAP）。然而，尽管经过数十年的研究，我们对这些必需蛋白质在细胞中如何发挥作用的了解仍然不完整。我们认为，ARF信号的内在复杂性及其由GEF和GAP进行的监管将需要许多实验室共同努力，最好是在一个联盟内以最佳方式汇集信息和资源。对这三个功能相关家族（≥70个哺乳动物基因）的合作研究将对细胞信号转导的调控产生变革性的见解。
Detailed structural, biochemical, cell biological, and genetic studies of any gene/protein are required to develop models of its actions in cells. Studying a protein family in the aggregate yields additional information, as one can include analyses of their coevolution, acquisition or loss of functionalities, structural pliability, and the emergence of shared or variations in molecular mechanisms. An even richer understanding of cell biology can be achieved through evaluating functionally linked protein families. In this review, we summarize current knowledge ofthreeprotein families: the ARF GTPases, the guanine nucleotide exchange factors (ARF GEFs) that activate them, and the GTPase-activating proteins (ARF GAPs) that have the ability to both propagate and terminate signaling. However, despite decades of scrutiny, our understanding of how these essential proteins function in cells remains fragmentary. We believe that the inherent complexity of ARF signaling and its regulation by GEFs and GAPs will require the concerted effort of many laboratories working together, ideally within a consortium to optimally pool information and resources. The collaborative study of these three functionally connected families (≥70 mammalian genes) will yield transformative insights into regulation of cell signaling.