AKT/PKB Signaling: Navigating the Network.
AKT/PKB Signaling: Navigating the Network.
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DOI：
10.1016/j.cell.2017.04.001
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发表时间：
2017-04-20
期刊：
影响因子：
64.5
通讯作者：
Toker A
中科院分区：
文献类型：
--
作者：
Manning BD;Toker A
Ser/Thr激酶AKT，也称为蛋白激酶B（PKB），在25年前被发现，并且一直是生物学和医学的不同领域中的数万项研究的焦点。我们对AKT上游调控输入的了解已经有了许多进展，关键的多功能下游信号节点（GSK 3，FoxO，mTORC 1），大大扩展了Akt的功能库，以及这种动态分支和循环信号网络的复杂电路，几乎在我们体内的每一个细胞中都存在。小鼠和人类遗传研究也揭示了AKT网络在几乎每个器官系统中的生理作用。考虑到AKT功能障碍在不同病理环境中的后果，包括发育和过度生长综合征、癌症、心血管疾病、胰岛素抵抗和2型糖尿病、炎症和自身免疫性疾病以及神经系统疾病，我们对AKT调节和功能的理解尤为重要。在开发AKT选择性小分子抑制剂方面也取得了很大进展。对AKT信号网络分子布线的深入了解继续产生跨越生物医学科学大多数学科的影响。
The Ser/Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of Akt, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body. Mouse and human genetic studies have also revealed physiological roles for the AKT network in nearly every organ system. Our comprehension of AKT regulation and functions is particularly important given the consequences of AKT dysfunction in diverse pathological settings, including developmental and overgrowth syndromes, cancer, cardiovascular disease, insulin resistance and type-2 diabetes, inflammatory and autoimmune disorders, and neurological disorders. There has also been much progress in developing AKT-selective small molecule inhibitors. Improved understanding of the molecular wiring of the AKT signaling network continues to make an impact that cuts across most disciplines of the biomedical sciences.
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