Department of Medical Biology, UiT-The Arctic University of Norway, N9037 Tromsoe, Norway.
Cancer Research UK Stress Response Laboratory, Medical Research Institute, Division of Cancer Research, Jacqui Wood Cancer Centre, James Arrot Drive, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom.
Front Biosci (Landmark Ed). 2016 Jan 1;21(2):374-84. doi: 10.2741/4394.
MAP kinase-activated protein kinase 5 (MK5) was first described as a downstream target of the p38 MAP kinase pathway leading to its alternative acronym of p38-regulated/activated protein kinase (PRAK). However, since the discovery that MK5 is a bona fide interaction partner of the atypical MAP kinases ERK3 and ERK4 and that this interaction leads to both the activation and subcellular relocalisation of MK5, there has been considerable debate as to the relative roles of these MAPK pathways in mediating the activation and biological functions of MK5. Here we discuss recent progress in defining novel upstream components of the ERK3/ERK4 signalling pathway, our increased understanding of the mechanism by which MK5 interacts with and is activated by ERK3 and ERK4, and the discovery of novel interaction partners for MK5. Finally, we review recent literature that suggests novel biological functions for MK5 in a range of physiological and pathophysiological conditions including neuronal function and cancer.
丝裂原活化蛋白激酶激活的蛋白激酶 5（MK5）最初被描述为 p38 丝裂原活化蛋白激酶途径的下游靶标，因此其另一个缩写为 p38 调节/激活蛋白激酶（PRAK）。然而，自从发现 MK5 是非典型丝裂原活化蛋白激酶 ERK3 和 ERK4 的真正相互作用伙伴，并且这种相互作用导致 MK5 的激活和亚细胞重新定位以来，关于这些 MAPK 途径在介导 MK5 的激活和生物学功能方面的相对作用一直存在相当大的争议。在这里，我们讨论了定义 ERK3/ERK4 信号通路新的上游成分的最新进展，我们对 MK5 与 ERK3 和 ERK4 相互作用并被其激活的机制的理解的提高，以及对 MK5 的新相互作用伙伴的发现。最后，我们回顾了最近的文献，这些文献表明 MK5 在一系列生理和病理生理条件下具有新的生物学功能，包括神经元功能和癌症。
