Wada Teiji, Penninger Josef M
IMBA: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr Bohr-gasse3-5, Vienna A-1030, Austria.
Oncogene. 2004 Apr 12;23(16):2838-49. doi: 10.1038/sj.onc.1207556.
Cells are continuously exposed to a variety of environmental stresses and have to decide 'to be or not to be' depending on the types and strength of stress. Among the many signaling pathways that respond to stress, mitogen-activated protein kinase (MAPK) family members are crucial for the maintenance of cells. Three subfamilies of MAPKs have been identified: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38-MAPKs. It has been originally shown that ERKs are important for cell survival, whereas JNKs and p38-MAPKs were deemed stress responsive and thus involved in apoptosis. However, the regulation of apoptosis by MAPKs is more complex than initially thought and often controversial. In this review, we discuss MAPKs in apoptosis regulation with attention to mouse genetic models and critically point out the multiple roles of MAPKs.
细胞持续暴露于各种环境应激中，必须根据应激的类型和强度决定“生存还是死亡”。在众多对应激作出反应的信号通路中，丝裂原活化蛋白激酶（MAPK）家族成员对于细胞的维持至关重要。已鉴定出MAPK的三个亚家族：细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38-MAPK。最初表明，ERK对细胞存活很重要，而JNK和p38-MAPK被认为是应激反应性的，因此参与细胞凋亡。然而，MAPK对细胞凋亡的调节比最初认为的更为复杂，且常常存在争议。在本综述中，我们讨论MAPK在细胞凋亡调节中的作用，重点关注小鼠遗传模型，并批判性地指出MAPK的多种作用。
