Department of Molecular and Biomedical Sciences, The University of Maine, Orono, ME 04401, USA.
Graduate School in Biomedical Sciences and Engineering, The University of Maine, Orono, ME 04401, USA.
Int J Mol Sci. 2019 Jul 12;20(14):3427. doi: 10.3390/ijms20143427.
The extracellular signal-regulated kinases (ERKs) comprise a particular branch of the mitogen-activated protein kinase cascades (MAPK) that transmits extracellular signals into the intracellular environment to trigger cellular growth responses. Similar to other MAPK cascades, the MAPK-ERK pathway signals through three core kinases-Raf, MAPK/ERK kinase (MEK), and ERK-which drive the signaling mechanisms responsible for the induction of cellular responses from extracellular stimuli including differentiation, proliferation, and cellular survival. However, pathogens like DNA viruses alter MAPK-ERK signaling in order to access DNA replication machineries, induce a proliferative state in the cell, or even prevent cell death mechanisms in response to pathogen recognition. Differential utilization of this pathway by multiple DNA viruses highlights the dynamic nature of the MAPK-ERK pathway within the cell and the importance of its function in regulating a wide variety of cellular fates that ultimately influence viral infection and, in some cases, result in tumorigenesis.
细胞外信号调节激酶(ERK)是丝裂原活化蛋白激酶(MAPK)级联途径中的一个特殊分支,可将细胞外信号传入细胞内环境,从而触发细胞生长反应。与其他 MAPK 级联途径类似,MAPK-ERK 途径通过三个核心激酶(Raf、MAPK/ERK 激酶(MEK)和 ERK)进行信号传递,这些激酶驱动着细胞对细胞外刺激做出反应的信号机制,包括分化、增殖和细胞存活。然而,DNA 病毒等病原体改变 MAPK-ERK 信号,以利用 DNA 复制机制,诱导细胞进入增殖状态,甚至防止细胞死亡机制,以应对病原体的识别。多种 DNA 病毒对该途径的不同利用,突出了 MAPK-ERK 途径在细胞内的动态性质及其在调节多种细胞命运中的重要性,这些命运最终影响病毒感染,在某些情况下,导致肿瘤发生。