Sumbayev V V, Yasinska I M
Department of Biochemistry, Mechnikov Odessa National University, Odessa, Ukraine.
Scand J Immunol. 2006 Jun;63(6):391-400. doi: 10.1111/j.1365-3083.2006.001764.x.
Mitogen-activated protein (MAP) kinase cascades are multifunctional signalling networks that influence cell growth, differentiation, apoptosis and cellular responses to stress. Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase that triggers apoptogenic kinase cascade leading to the phosphorylation/activation of c-Jun N-terminal kinases (JNK) and p38-MAP kinase, which are responsible to induce apoptotic cell death. This pathway plays a pivotal role in the transduction of signals from different apoptotic stimuli. Recently, it has become evident that ASK1 and its downstream pathway are employed in the transduction of signals from Toll-like receptors (TLR) - multistep processes that interfere with different intracellular signalling pathways. TLR are the key proteins that allow mammals to detect pathogens and mediate innate immune responses. In addition, ASK1 and its downstream pathway play a target role in the regulation of apoptosis in some cases of viral infection - AIDS, influenza, hepatitis C and others. In the present review, we summarize current knowledge about the role of ASK1 and its downstream pathway in innate immune responses and viral infection.
丝裂原活化蛋白（MAP）激酶级联反应是多功能信号网络，影响细胞生长、分化、凋亡以及细胞对应激的反应。凋亡信号调节激酶1（ASK1）是一种MAP激酶激酶激酶，它触发导致c-Jun氨基末端激酶（JNK）和p38-MAP激酶磷酸化/激活的凋亡激酶级联反应，这两种激酶负责诱导凋亡性细胞死亡。该途径在来自不同凋亡刺激的信号转导中起关键作用。最近，很明显ASK1及其下游途径参与了来自Toll样受体（TLR）信号的转导——这是干扰不同细胞内信号通路的多步骤过程。TLR是使哺乳动物能够检测病原体并介导先天免疫反应的关键蛋白。此外，在某些病毒感染——艾滋病、流感、丙型肝炎等病例中，ASK1及其下游途径在细胞凋亡调节中起靶向作用。在本综述中，我们总结了关于ASK1及其下游途径在先天免疫反应和病毒感染中作用的当前知识。
