Perander Maria, Keyse Stephen M, Seternes Ole-Morten
Department of Pharmacology, Institute of Medical Biology, University of Tromso, N-9037 Tromso, Norway.
Front Biosci. 2008 May 1;13:4617-24. doi: 10.2741/3027.
MAP kinase-activated protein kinase 5 (MK5) was originally described as a protein kinase activated downstream of the p38 MAP kinase and is also named p38-regulated/activated protein kinase (PRAK). However, while MK5 is most similar in sequence to the two p38 regulated MAPKAP kinases MK2 and MK3, recent data has shown that in contrast to these enzymes MK5 is not activated in response to either cellular stress or pro-inflammatory cytokines. This lack of response to stimuli which cause robust activation of p38 MAP kinase in vivo is supported by data obtained using transgenic mice lacking MK5. Unlike animals lacking MK2 and MK3, MK5 null mice respond normally to endotoxic shock and display an unchanged pattern of cytokine expression in response to LPS. Clues as to the physiological function of MK5 have come from the recent observation that MK5 is uniquely regulated and activated following complex formation with the atypical MAP kinases ERK3 and ERK4. Thus, it is possible that MK5 is unique amongst the MAPKAP kinases in being regulated downstream of signaling pathways other than the classical MAP kinases p38 and ERK1/2.
丝裂原活化蛋白激酶激活的蛋白激酶5（MK5）最初被描述为一种在p38丝裂原活化蛋白激酶下游被激活的蛋白激酶，也被称为p38调节/激活蛋白激酶（PRAK）。然而，虽然MK5在序列上与两种p38调节的丝裂原活化蛋白激酶相关激酶MK2和MK3最为相似，但最近的数据表明，与这些酶不同的是，MK5不会因细胞应激或促炎细胞因子而被激活。使用缺乏MK5的转基因小鼠获得的数据支持了这种在体内对导致p38丝裂原活化蛋白激酶强烈激活的刺激缺乏反应的情况。与缺乏MK2和MK3的动物不同，MK5基因敲除小鼠对内毒素休克反应正常，并且在对脂多糖的反应中细胞因子表达模式不变。关于MK5生理功能的线索来自最近的观察结果，即MK5在与非典型丝裂原活化蛋白激酶ERK3和ERK4形成复合物后受到独特的调节和激活。因此，MK5有可能在丝裂原活化蛋白激酶相关激酶中是独特的，它在除经典丝裂原活化蛋白激酶p38和ERK1/2之外的信号通路下游受到调节。
