Kim Eun Kyung, Choi Eui-Ju
Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, South Korea.
Arch Toxicol. 2015 Jun;89(6):867-82. doi: 10.1007/s00204-015-1472-2. Epub 2015 Feb 18.
The mitogen-activated protein kinases (MAPKs) in mammals include c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK). These enzymes are serine-threonine protein kinases that regulate various cellular activities including proliferation, differentiation, apoptosis or survival, inflammation, and innate immunity. The compromised MAPK signaling pathways contribute to the pathology of diverse human diseases including cancer and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The JNK and p38 MAPK signaling pathways are activated by various types of cellular stress such as oxidative, genotoxic, and osmotic stress as well as by proinflammatory cytokines such as tumor necrosis factor-α and interleukin 1β. The Ras-Raf-MEK-ERK signaling pathway plays a key role in cancer development through the stimulation of cell proliferation and metastasis. The p38 MAPK pathway contributes to neuroinflammation mediated by glial cells including microglia and astrocytes, and it has also been associated with anticancer drug resistance in colon and liver cancer. We here summarize recent research on the roles of MAPK signaling pathways in human diseases, with a focus on cancer and neurodegenerative conditions.
哺乳动物中的丝裂原活化蛋白激酶（MAPK）包括c-Jun氨基末端激酶（JNK）、p38 MAPK和细胞外信号调节激酶（ERK）。这些酶是丝氨酸-苏氨酸蛋白激酶，可调节各种细胞活动，包括增殖、分化、凋亡或存活、炎症和先天免疫。受损的MAPK信号通路会导致多种人类疾病的病理过程，包括癌症和神经退行性疾病，如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。JNK和p38 MAPK信号通路可被多种类型的细胞应激激活，如氧化应激、基因毒性应激和渗透压应激，以及促炎细胞因子，如肿瘤坏死因子-α和白细胞介素1β。Ras-Raf-MEK-ERK信号通路通过刺激细胞增殖和转移在癌症发展中起关键作用。p38 MAPK通路参与由包括小胶质细胞和星形胶质细胞在内的胶质细胞介导的神经炎症，并且还与结肠癌和肝癌中的抗癌药物耐药性有关。我们在此总结了关于MAPK信号通路在人类疾病中的作用的最新研究，重点是癌症和神经退行性疾病。
