Sánchez I, Hughes R T, Mayer B J, Yee K, Woodgett J R, Avruch J, Kyriakis J M, Zon L I
Diabetes Research Laboratory, Massachusetts General Hospital East, Charlestown.
Nature. 1994;372(6508):794-8. doi: 10.1038/372794a0.
The stress-activated protein kinases (SAPKs), which are distantly related to the MAP kinases, are the dominant c-Jun amino-terminal protein kinases activated in response to a variety of cellular stresses, including treatment with tumour-necrosis factor-alpha and interleukin-beta (refs 1, 2). SAPK phosphorylation of c-Jun probably activates the c-Jun transactivation function. SAPKs are part of a signal transduction cascade related to, but distinct from, the MAPK pathway. We have now identified a novel protein kinase, called SAPK/ERK kinase-1 (SEK1), which is structurally related to the MAP kinase kinases (MEKs). SEK1 is a potent activator of the SAPKs in vitro and in vivo. An inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK pathway. Although alternative mechanisms of SAPK activation may exist, as an immediate upstream activator of the SAPKs, SEK1 further defines a signalling cascade that couples cellular stress agonists to the c-Jun transcription factor.
应激激活蛋白激酶（SAPK）与丝裂原活化蛋白激酶（MAPK）有较远的亲缘关系，是在多种细胞应激反应中被激活的主要c-Jun氨基末端蛋白激酶，这些应激包括用肿瘤坏死因子-α和白细胞介素-β处理（参考文献1、2）。c-Jun的SAPK磷酸化可能激活c-Jun反式激活功能。SAPK是与MAPK途径相关但不同的信号转导级联反应的一部分。我们现已鉴定出一种名为SAPK/ERK激酶-1（SEK1）的新型蛋白激酶，它在结构上与MAP激酶激酶（MEK）相关。SEK1在体外和体内都是SAPK的有效激活剂。一种无活性的SEK1突变体可阻断细胞外刺激引起的SAPK激活，而不干扰MAPK途径。尽管可能存在SAPK激活的其他机制，但作为SAPK的直接上游激活剂，SEK1进一步定义了一个将细胞应激激动剂与c-Jun转录因子偶联的信号级联反应。
