Tibaldi Elena, Federti Enrica, Matte Alessandro, Iatcenko Iana, Wilson Anand B, Riccardi Veronica, Pagano Mario Angelo, De Franceschi Lucia
Department of Molecular Medicine, University of Padua, 35131 Padua, Italy.
Department of Medicine, University of Verona and AOUI Verona, 37134 Verona, Italy.
Antioxidants (Basel). 2020 Apr 24;9(4):353. doi: 10.3390/antiox9040353.
The dynamic coordination between kinases and phosphatases is crucial for cell homeostasis, in response to different stresses. The functional connection between oxidation and the intracellular signaling machinery still remains to be investigated. In the last decade, several studies have highlighted the role of reactive oxygen species (ROS) as modulators directly targeting kinases, phosphatases, and downstream modulators, or indirectly acting on cysteine residues on kinases/phosphatases resulting in protein conformational changes with modulation of intracellular signaling pathway(s). Translational studies have revealed the important link between oxidation and signal transduction pathways in hematological disorders. The intricate nature of intracellular signal transduction mechanisms, based on the generation of complex networks of different types of signaling proteins, revealed the novel and important role of phosphatases together with kinases in disease mechanisms. Thus, therapeutic approaches to abnormal signal transduction pathways should consider either inhibition of overactivated/accumulated kinases or homeostatic signaling resetting through the activation of phosphatases. This review discusses the progress in the knowledge of the interplay between oxidation and cell signaling, involving phosphatase/kinase systems in models of globally distributed hematological disorders.
激酶和磷酸酶之间的动态协调对于细胞稳态至关重要，以应对不同的应激。氧化与细胞内信号传导机制之间的功能联系仍有待研究。在过去十年中，多项研究强调了活性氧（ROS）作为直接靶向激酶、磷酸酶和下游调节因子的调节剂的作用，或间接作用于激酶/磷酸酶上的半胱氨酸残基，导致蛋白质构象变化，从而调节细胞内信号通路。转化研究揭示了氧化与血液系统疾病中信号转导通路之间的重要联系。基于不同类型信号蛋白复杂网络的产生，细胞内信号转导机制的复杂性揭示了磷酸酶与激酶在疾病机制中的新的重要作用。因此，针对异常信号转导通路的治疗方法应考虑抑制过度激活/积累的激酶或通过激活磷酸酶来重置稳态信号。本综述讨论了在全球分布的血液系统疾病模型中，氧化与细胞信号传导之间相互作用的知识进展，涉及磷酸酶/激酶系统。
