Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5
Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5
复制标题
DOI：
10.1074/jbc.m606693200
复制
发表时间：
2006-11-17
影响因子：
4.8
通讯作者：
Gaestel, Matthias
中科院分区：
文献类型：
--
作者：
Kant, Shashi;Schumacher, Stefanie;Gaestel, Matthias
细胞外调节激酶（ERK） 4 （MAPK4）和ERK3 （MAPK6）是结构相关的非典型MAPKs，仅在c端延伸上表现出主要差异。ERK3是一种不稳定的细胞质蛋白，可结合、易位和激活mapk激活的蛋白激酶（MK） 5。在这里，我们研究了ERK4的稳定性和表达，并分析了其结合、转运和激活MK5的能力。我们发现，与ERK3不同，ERK4是一种与内源性MK5结合的稳定蛋白。ERK4与MK5的相互作用导致MK5易位到细胞质并通过磷酸化激活。在转染的HEK293细胞中，过表达的催化死亡的ERK3能够激活MK5， ERK4的催化活性是激活MK5所必需的，这表明ERK4直接磷酸化MK5。有趣的是，ERK4与ERK3二聚和/或寡聚，表明过表达的失活ERK3将活跃的内源性ERK4招募到MK5激活。因此，ERK3和ERK4协同激活MK5。
The extracellular-regulated kinase (ERK) 4 (MAPK4) and ERK3 (MAPK6) are structurally related atypical MAPKs displaying major differences only in the C-terminal extension. ERK3 is known as an unstable mostly cytoplasmic protein that binds, translocates, and activates the MAPK-activated protein kinase (MK) 5. Here we have investigated the stability and expression of ERK4 and have analyzed its ability to bind, translocate, and activate MK5. We show that, in contrast to ERK3, ERK4 is a stable protein that binds to endogenous MK5. Interaction of ERK4 with MK5 leads to translocation of MK5 to the cytoplasm and to its activation by phosphorylation. In transfected HEK293 cells, where overexpressed catalytically dead ERK3 is able to activate MK5, catalytic activity of ERK4 is necessary for activation of MK5, indicating that ERK4 directly phosphorylates MK5. Interestingly, ERK4 dimerizes and/or oligomerizes with ERK3, suggesting that overexpressed inactive ERK3 recruits active endogenous ERK4 to MK5 for its activation. Hence, ERK3 and ERK4 cooperate in activation of MK5.