在亚细胞隔室中对 AMPK 信号的空间控制。
Spatial control of AMPK signaling at subcellular compartments.
机构信息
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
出版信息
Crit Rev Biochem Mol Biol. 2020 Feb;55(1):17-32. doi: 10.1080/10409238.2020.1727840. Epub 2020 Feb 18.
Abstract
AMP-activated protein kinase (AMPK) is a master regulator of energy homeostasis that functions to restore the energy balance by phosphorylating its substrates during altered metabolic conditions. AMPK activity is tightly controlled by diverse regulators including its upstream kinases LKB1 and CaMKK2. Recent studies have also identified the localization of AMPK at different intracellular compartments as another key mechanism for regulating AMPK signaling in response to specific stimuli. This review discusses the AMPK signaling associated with different subcellular compartments, including lysosomes, endoplasmic reticulum, mitochondria, Golgi apparatus, nucleus, and cell junctions. Because altered AMPK signaling is associated with various pathologic conditions including cancer, targeting AMPK signaling in different subcellular compartments may present attractive therapeutic approaches for treatment of disease.
摘要
腺苷酸活化蛋白激酶（AMPK）是能量平衡的主要调节剂，其功能是在代谢改变的情况下通过磷酸化其底物来恢复能量平衡。AMPK 的活性受到多种调节剂的严格控制，包括上游激酶 LKB1 和 CaMKK2。最近的研究还发现，AMPK 在不同的细胞内隔室中的定位是另一种调节 AMPK 信号响应特定刺激的关键机制。本综述讨论了与不同细胞内隔室相关的 AMPK 信号，包括溶酶体、内质网、线粒体、高尔基体、细胞核和细胞连接。因为改变的 AMPK 信号与包括癌症在内的各种病理状况有关，因此靶向不同细胞内隔室的 AMPK 信号可能为疾病的治疗提供有吸引力的治疗方法。
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2
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3
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4
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