Hardie D Grahame, Scott John W, Pan David A, Hudson Emma R
Division of Molecular Physiology, Wellcome Trust Biocentre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
FEBS Lett. 2003 Jul 3;546(1):113-20. doi: 10.1016/s0014-5793(03)00560-x.
The AMP-activated protein kinase is a sensor of cellular energy status that is found in all eukaryotic cells. It is activated by rising AMP and falling ATP by a complex mechanism that results in an ultrasensitive response. The functions of the different domains on the three subunits of the alphabetagamma heterotrimer are slowly being unravelled, and a recent development has been the identification of a glycogen-binding domain on the beta subunit. Along with findings that high cellular glycogen represses kinase activation, this suggests that the system may be a sensor of glycogen content as well as of AMP and ATP. New insights have been obtained into the sequence and structural features by which the kinase recognises its downstream target proteins, and these are discussed. Once activated by depletion of cellular energy reserves, the kinase switches on ATP-producing catabolic pathways and switches off ATP-consuming processes, both via direct phosphorylation of regulatory proteins and via indirect effects on gene expression. A survey of the range of downstream targets for this important signalling pathway is presented.
AMP 激活的蛋白激酶是一种存在于所有真核细胞中的细胞能量状态传感器。它通过一种复杂机制被升高的 AMP 和降低的 ATP 激活，从而产生超敏反应。字母γ异源三聚体三个亚基上不同结构域的功能正逐渐被揭示，最近的一项进展是在β亚基上鉴定出一个糖原结合结构域。连同高细胞糖原抑制激酶激活的研究结果，这表明该系统可能是糖原含量以及 AMP 和 ATP 的传感器。关于激酶识别其下游靶蛋白的序列和结构特征已获得新的见解，并将对此进行讨论。一旦细胞能量储备耗尽而被激活，该激酶会通过对调节蛋白的直接磷酸化以及对基因表达的间接影响，开启产生 ATP 的分解代谢途径并关闭消耗 ATP 的过程。本文还对这一重要信号通路的下游靶标范围进行了综述。
