Gaestel Matthias
Department of Biochemistry, Hannover Medical School, Carl-Neuberg-Str. 1, D30625 Hannover, Germany.
Front Biosci. 2008 May 1;13:6050-9. doi: 10.2741/3136.
Within the signalling network of mammalian cells, MAPK-activated protein kinases (MAPKAPKs) have been identified downstream to various MAPKs, such as the classical MAPKs, ERK1/2, the stress-activated p38 MAPKs and the atypical MAPKs ERK3/4/5. Here, the current understanding of the specificity of MAPK to MAPKAPK signalling, the underlying mechanisms of protein-protein-interaction and the effects on subcellular localisation are reviewed. It is demonstrated that specificity in this signalling section is maintained by protein domain interactions and by regulated subcellular localisation. These mechanisms enable specific MAPK pathways to act independently via specific MAPKAPKs but also allow different MAPK pathways to cooperate in downstream signalling in a coordinated fashion.
在哺乳动物细胞的信号网络中，丝裂原活化蛋白激酶激活的蛋白激酶（MAPKAPK）已被确定位于各种丝裂原活化蛋白激酶（MAPK）的下游，如经典的MAPK、细胞外信号调节激酶1/2（ERK1/2）、应激激活的p38 MAPK和非典型的MAPK ERK3/4/5。本文综述了目前对MAPK与MAPKAPK信号特异性、蛋白质-蛋白质相互作用的潜在机制以及对亚细胞定位影响的理解。结果表明，该信号传导部分的特异性通过蛋白质结构域相互作用和亚细胞定位调控得以维持。这些机制使特定的MAPK途径能够通过特定的MAPKAPK独立发挥作用，同时也允许不同的MAPK途径以协调的方式在下游信号传导中协同作用。
