Heitmann Tyler, Barrow James C
Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, 725 North Wolfe Street Suite 300, Baltimore, MD 21205, USA.
The Lieber Institute for Brain Development, 855 North Wolfe Street Suite 300, Baltimore, MD 21205, USA.
Biomolecules. 2023 Aug 28;13(9):1317. doi: 10.3390/biom13091317.
Inositol is a unique biological small molecule that can be phosphorylated or even further pyrophosphorylated on each of its six hydroxyl groups. These numerous phosphorylation states of inositol along with the kinases and phosphatases that interconvert them comprise the inositol phosphate signaling pathway. Inositol hexakisphosphate kinases, or IP6Ks, convert the fully mono-phosphorylated inositol to the pyrophosphate 5-IP7 (also denoted IP7). There are three isoforms of IP6K: IP6K1, 2, and 3. Decades of work have established a central role for IP6Ks in cell signaling. Genetic and pharmacologic manipulation of IP6Ks in vivo and in vitro has shown their importance in metabolic disease, chronic kidney disease, insulin signaling, phosphate homeostasis, and numerous other cellular and physiologic processes. In addition to these peripheral processes, a growing body of literature has shown the role of IP6Ks in the central nervous system (CNS). IP6Ks have a key role in synaptic vesicle regulation, Akt/GSK3 signaling, neuronal migration, cell death, autophagy, nuclear translocation, and phosphate homeostasis. IP6Ks' regulation of these cellular processes has functional implications in vivo in behavior and CNS anatomy.
肌醇是一种独特的生物小分子，其六个羟基中的每一个都可以被磷酸化，甚至进一步焦磷酸化。肌醇的这些众多磷酸化状态以及使它们相互转化的激酶和磷酸酶构成了肌醇磷酸信号通路。肌醇六磷酸激酶（IP6Ks）将完全单磷酸化的肌醇转化为焦磷酸5-IP7（也称为IP7）。IP6K有三种亚型：IP6K1、2和3。数十年来的研究已证实IP6Ks在细胞信号传导中起核心作用。体内和体外对IP6Ks进行基因和药理学操作已表明它们在代谢性疾病、慢性肾病、胰岛素信号传导、磷酸盐稳态以及许多其他细胞和生理过程中的重要性。除了这些外周过程外，越来越多的文献表明IP6Ks在中枢神经系统（CNS）中的作用。IP6Ks在突触小泡调节、Akt/GSK3信号传导、神经元迁移、细胞死亡、自噬、核转位和磷酸盐稳态中起关键作用。IP6Ks对这些细胞过程的调节在行为和CNS解剖结构的体内功能中具有重要意义。
