Paul A, Wilson S, Belham C M, Robinson C J, Scott P H, Gould G W, Plevin R
Department of Physiology and Pharmacology, Royal College, University of Strathclyde, Glasgow.
Cell Signal. 1997 Sep;9(6):403-10. doi: 10.1016/s0898-6568(97)00042-9.
The response of cells to extracellular stimuli is mediated in part by a number of intracellular kinase and phosphatase enzymes. Within this area of research the activation of the p42 and p44 isoforms of mitogen-activated protein (MAP) kinases have been extensively described and characterised as central components of the signal transduction pathways stimulated by both growth factors and G-protein-coupled receptor agonists. Signaling events mediated by these kinases are fundamental to cellular functions such as proliferation and differentiation. More recently, homologues of the p42 and p44 isoforms of MAP kinase have been described, namely the stress-activated protein kinases (SAPKs) or alternatively the c-jun N-terminal kinases (JNKs) and p38 MAP kinase (the mammalian homologue of yeast HOG1). These MAP kinase homologues are integral components of parallel MAP kinase cascades activated in response to a number of cellular stresses including inflammatory cytokines (e.g., Interleukin-1 (Il-1) and tumour necrosis factor-alpha (TNF-alpha), heat and chemical shock, bacterial endotoxin and ischaemia/cellular ATP depletion. Activation of these MAP kinase homologues mediates the transduction of extracellular signals to the nucleus and are pivotal events in the regulation of the transcription events that determine functional outcome in response to such stresses. In this review we highlight the identification and characterisation of the stress-activated MAP kinase homologues, their role as components of parallel MAP kinase pathways and the regulation of cellular responses following exposure to cellular stress.
细胞对细胞外刺激的反应部分是由多种细胞内激酶和磷酸酶介导的。在该研究领域中，有丝分裂原激活蛋白（MAP）激酶的p42和p44亚型的激活已得到广泛描述，并被确定为生长因子和G蛋白偶联受体激动剂所刺激的信号转导途径的核心组成部分。由这些激酶介导的信号事件对于细胞增殖和分化等细胞功能至关重要。最近，已描述了MAP激酶p42和p44亚型的同源物，即应激激活蛋白激酶（SAPK），或者称为c-jun氨基末端激酶（JNK）和p38 MAP激酶（酵母HOG1的哺乳动物同源物）。这些MAP激酶同源物是平行MAP激酶级联反应的组成部分，在响应多种细胞应激时被激活，这些应激包括炎性细胞因子（例如，白细胞介素-1（Il-1）和肿瘤坏死因子-α（TNF-α））、热和化学休克、细菌内毒素以及缺血/细胞ATP耗竭。这些MAP激酶同源物的激活介导细胞外信号向细胞核的转导，并且是调节转录事件的关键环节，这些转录事件决定了对这种应激的功能反应。在本综述中，我们重点介绍了应激激活的MAP激酶同源物的鉴定和特性、它们作为平行MAP激酶途径组成部分的作用以及细胞暴露于细胞应激后细胞反应的调节。
