New insights into the activation, interaction partners and possible functions of MK5/PRAK

TY - JOUR

T1 - New insights into the activation, interaction partners and possible functions of MK5/PRAK

AU - Perander, Maria

AU - Keyse, Stephen M.

AU - Seternes, Ole-Morten

N1 - Work in the Keyse laboratory is supported by a programme grant from Cancer Research UK (CR-UK Stress Response Laboratory C8227/A12053). Work in the Seternes laboratory is supported by grant from the Aakre foundation.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Cytoplasm

KW - Enzyme activation

KW - Humans

KW - Intracellular signaling peptides and proteins

KW - Phosphorylation

KW - Protein binding

KW - Protein-Serine-Threonine Kinases

KW - Signal transduction

KW - Substrate specificity

KW - Journal article

KW - Research support, Non-U.S. Gov't

KW - Review

U2 - 10.2741/4394

DO - 10.2741/4394

M3 - Article

C2 - 26709779

SN - 1093-9946

VL - 21

SP - 374

EP - 384

JO - Frontiers in Bioscience-Landmark

JF - Frontiers in Bioscience-Landmark

IS - 2

ER -