Antal Corina E, Newton Alexandra C
*Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093, U.S.A.
Biochem Soc Trans. 2014 Dec;42(6):1477-83. doi: 10.1042/BST20140172.
Precise control of the amplitude of protein kinase C (PKC) signalling is essential for cellular homoeostasis, and disruption of this control leads to pathophysiological states such as cancer, neurodegeneration and diabetes. For conventional and novel PKC, this amplitude is meticulously tuned by multiple inputs that regulate the amount of enzyme in the cell, its ability to sense its allosteric activator diacylglycerol, and protein scaffolds that co-ordinate access to substrates. Key to regulation of the signalling output of most PKC isoenzymes is the ability of cytosolic enzyme to respond to the membrane-embedded lipid second messenger, diacylglycerol, in a dynamic range that prevents signalling in the absence of agonists but allows efficient activation in response to small changes in diacylglycerol levels. The present review discusses the regulatory inputs that control the spatiotemporal dynamics of PKC signalling, with a focus on conventional and novel PKC isoenzymes.
精确控制蛋白激酶C（PKC）信号的幅度对于细胞内稳态至关重要，而这种控制的破坏会导致诸如癌症、神经退行性变和糖尿病等病理生理状态。对于传统型和新型PKC而言，该幅度是通过多种输入进行精确调节的，这些输入调节细胞内酶的数量、其感知变构激活剂二酰基甘油的能力以及协调底物获取的蛋白质支架。大多数PKC同工酶信号输出调节的关键在于胞质酶能够在动态范围内对膜嵌入的脂质第二信使二酰基甘油作出反应，该动态范围可防止在没有激动剂的情况下发出信号，但允许对二酰基甘油水平的微小变化作出有效激活反应。本综述讨论了控制PKC信号时空动态的调节输入，重点是传统型和新型PKC同工酶。
