Aggarwal-Howarth Stacey, Scott John D
Howard Hughes Medical Institute and Department of Pharmacology, University of Washington, Seattle, WA, U.S.A.
Biochem Soc Trans. 2017 Apr 15;45(2):371-379. doi: 10.1042/BST20160329.
Pseudokinases and pseudophosphatases possess the ability to bind substrates without catalyzing their modification, thereby providing a mechanism to recruit potential phosphotargets away from active enzymes. Since many of these pseudoenzymes possess other characteristics such as localization signals, separate catalytic sites, and protein-protein interaction domains, they have the capacity to influence signaling dynamics in local environments. In a similar manner, the targeting of signaling enzymes to subcellular locations by A-kinase-anchoring proteins (AKAPs) allows for precise and local control of second messenger signaling events. Here, we will discuss how pseudoenzymes form 'pseudoscaffolds' and compare and contrast this compartment-specific regulatory role with the signal organization properties of AKAPs. The mitochondria will be the focus of this review, as they are dynamic organelles that influence a broad range of cellular processes such as metabolism, ATP synthesis, and apoptosis.
假激酶和假磷酸酶具有在不催化底物修饰的情况下结合底物的能力,从而提供一种将潜在磷酸化靶点从活性酶中招募出来的机制。由于许多这类假酶具有其他特征,如定位信号、独立的催化位点和蛋白质-蛋白质相互作用结构域,它们有能力影响局部环境中的信号转导动态。同样,A激酶锚定蛋白(AKAPs)将信号酶靶向亚细胞位置,使得第二信使信号事件能够得到精确的局部控制。在此,我们将讨论假酶如何形成“假支架”,并将这种特定区室的调节作用与AKAPs的信号组织特性进行比较和对比。线粒体将成为本综述的重点,因为它们是动态细胞器,影响着广泛的细胞过程,如代谢、ATP合成和细胞凋亡。