Kim Eun Kyung, Choi Eui-Ju
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
Biochim Biophys Acta. 2010 Apr;1802(4):396-405. doi: 10.1016/j.bbadis.2009.12.009. Epub 2010 Jan 14.
The mammalian family of mitogen-activated protein kinases (MAPKs) includes extracellular signal-regulated kinase (ERK), p38, and c-Jun NH(2)-terminal kinase (JNK), with each MAPK signaling pathway consisting of at least three components, a MAPK kinase kinase (MAP3K), a MAPK kinase (MAP2K), and a MAPK. The MAPK pathways are activated by diverse extracellular and intracellular stimuli including peptide growth factors, cytokines, hormones, and various cellular stressors such as oxidative stress and endoplasmic reticulum stress. These signaling pathways regulate a variety of cellular activities including proliferation, differentiation, survival, and death. Deviation from the strict control of MAPK signaling pathways has been implicated in the development of many human diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and various types of cancers. Persistent activation of the JNK or p38 signaling pathways has been suggested to mediate neuronal apoptosis in AD, PD, and ALS, whereas the ERK signaling pathway plays a key role in several steps of tumorigenesis including cancer cell proliferation, migration, and invasion. In this review, we summarize recent findings on the roles of MAPK signaling pathways in human disorders, focusing on cancer and neurodegenerative diseases including AD, PD, and ALS.
丝裂原活化蛋白激酶（MAPK）的哺乳动物家族包括细胞外信号调节激酶（ERK）、p38和c-Jun氨基末端激酶（JNK），每条MAPK信号通路至少由三个组分组成，即MAPK激酶激酶（MAP3K）、MAPK激酶（MAP2K）和MAPK。MAPK通路可被多种细胞外和细胞内刺激激活，包括肽生长因子、细胞因子、激素以及各种细胞应激源，如氧化应激和内质网应激。这些信号通路调节多种细胞活动，包括增殖、分化、存活和死亡。MAPK信号通路的严格控制出现偏差与许多人类疾病的发生有关，包括阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化症（ALS）和各种类型的癌症。JNK或p38信号通路的持续激活被认为介导了AD、PD和ALS中的神经元凋亡，而ERK信号通路在肿瘤发生的几个步骤中起关键作用，包括癌细胞的增殖、迁移和侵袭。在本综述中，我们总结了关于MAPK信号通路在人类疾病中作用的最新发现，重点关注癌症和神经退行性疾病，包括AD、PD和ALS。
