Institute for Molecular Bioscience (IMB) and Centre for Inflammation and Disease Research, The University of Queensland, St Lucia, QLD 4072, Australia.
Biochem Soc Trans. 2022 Oct 31;50(5):1341-1352. doi: 10.1042/BST20220271.
Extracellular signal-related kinases 1 and 2 (ERK1/2) are the final components of the mitogen-activated protein kinase (MAPK) phosphorylation cascade, an integral module in a diverse array of signalling pathways for shaping cell behaviour and fate. More recently, studies have shown that ERK1/2 plays an essential role downstream of immune receptors to elicit inflammatory gene expression in response to infection and cell or tissue damage. Much of this work has studied ERK1/2 activation in Toll-like receptor (TLR) pathways, providing mechanistic insights into its recruitment, compartmentalisation and activation in cells of the innate immune system. In this review, we summarise the typical activation of ERK1/2 in growth factor receptor pathways before discussing its known roles in immune cell signalling with a focus downstream of TLRs. We examine emerging research uncovering evidence of dysfunctional ERK1/2 signalling in inflammatory diseases and discuss the potential therapeutic benefit of targeting ERK1/2 pathways in inflammation.
细胞外信号相关激酶 1 和 2(ERK1/2)是丝裂原活化蛋白激酶(MAPK)磷酸化级联反应的最终成分,是细胞行为和命运形成的各种信号通路的一个组成模块。最近的研究表明,ERK1/2 在免疫受体下游发挥重要作用,以响应感染和细胞或组织损伤引发炎症基因表达。这项工作的大部分都研究了 Toll 样受体(TLR)途径中的 ERK1/2 激活,为其在先天免疫系统细胞中的募集、区室化和激活提供了机制上的见解。在这篇综述中,我们总结了生长因子受体途径中 ERK1/2 的典型激活,然后讨论了其在免疫细胞信号转导中的已知作用,重点是 TLR 下游的作用。我们研究了揭示炎症性疾病中 ERK1/2 信号传导功能障碍的新研究,并讨论了靶向 ERK1/2 通路在炎症中的潜在治疗益处。