Department of Structural Biology of Signaling Proteins, Division BIOCEV, Institute of Physiology of the Czech Academy of Sciences, 25250 Vestec, Czech Republic.
Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, 12843 Prague, Czech Republic.
Int J Mol Sci. 2020 Nov 21;21(22):8824. doi: 10.3390/ijms21228824.
Phosphorylation by kinases governs many key cellular and extracellular processes, such as transcription, cell cycle progression, differentiation, secretion and apoptosis. Unsurprisingly, tight and precise kinase regulation is a prerequisite for normal cell functioning, whereas kinase dysregulation often leads to disease. Moreover, the functions of many kinases are regulated through protein-protein interactions, which in turn are mediated by phosphorylated motifs and often involve associations with the scaffolding and chaperon protein 14-3-3. Therefore, the aim of this review article is to provide an overview of the state of the art on 14-3-3-mediated kinase regulation, focusing on the most recent mechanistic insights into these important protein-protein interactions and discussing in detail both their structural aspects and functional consequences.
激酶的磷酸化作用控制着许多关键的细胞内和细胞外过程，如转录、细胞周期进程、分化、分泌和细胞凋亡。毫不奇怪，激酶的严格和精确调节是正常细胞功能的前提，而激酶失调常常导致疾病。此外，许多激酶的功能是通过蛋白质-蛋白质相互作用来调节的，而这些相互作用反过来又由磷酸化基序介导，并且通常涉及与支架和伴侣蛋白 14-3-3 的关联。因此，本文综述的目的是概述 14-3-3 介导的激酶调节的最新进展，重点介绍这些重要的蛋白质-蛋白质相互作用的最新机制见解，并详细讨论它们的结构和功能后果。
