Biological functions and role of mitogen-activated protein kinase activated protein kinase 2 (MK2) in inflammatory diseases

The p38/MK2 pathway regulates a wide range of biological functions, and thus has most been explored as a therapeutic target for inhibition of severe and chronic inflammatory diseases. Till date, several p38 inhibitors with potent anti-inflammatory effects in pre-clinical models have been discovered, but most of them have failed in clinics due to serious systemic toxicity issues. MK2 is a serine-threonine kinase downstream to p38 and is activated directly through phosphorylation of p38 under stress and inflammatory stimulus. MK2 has been shown to be a direct and essential component in regulating the biosynthesis of pro-inflammatory cytokines. Disruption of MK2 signaling leads to a significant reduction in the level of several pro-inflammatory cytokine production. For these reasons, MK2 has been identified as an alternate molecular target in order to block the pathway with an assumption that this approach would show similar efficacy as that of p38 inhibitors with lesser toxicity concerns. This review briefly summarizes the molecular structure of MK2 and major biological functions in context with its pharmacological modulation to address various inflammatory diseases. It also discusses the points of advantages over p38 inhibition along with recent update in the development of small molecule MK2 inhibitors. (C) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. zo.o. All rights reserved.