Targeting ERK3/MK5 complex for treatment of obesity and diabetes.

Kinases represent one of the largest druggable families of proteins. Importantly, many kinases are aberrantly activated/de-activated in multiple organs during obesity, which contributes to the development of diabetes and associated diseases. Previous results indicate that the complex between Extracellular-regulated kinase 3 (ERK3) and Mitogen-Activated Protein Kinase (MAPK)-activated protein kinase 5 (MK5) suppresses energy dissipation and promotes fatty acids (FAs) output in adipose tissue and, therefore promotes obesity and diabetes. However, the therapeutic potential of targeting this complex at the systemic level has not been fully explored. Here we applied a translational approach to target the ERK3/MK5 complex in mice. Importantly, deletion of ERK3 in the whole body or administration of MK5-specific inhibitor protects against obesity and promotes insulin sensitivity. Finally, we show that the expression of ERK3 and MK5 correlates with the degree of obesity and that ERK3/MK5 complex regulates energy dissipation in human adipocytes. Altogether, we demonstrate that ERK3/MK5 complex can be targeted in vivo to preserve metabolic health and combat obesity and diabetes.This study was funded by European Research Council (ERC) Starting Grant SicMetabol (no.678119), Emmy Noether Grant Su820/1-1 from the German Research Foundation (DFG), EMBO Installation Grant from European Molecular Biology Organization (EMBO), the Dioscuri Centre of Scientific Excellenced The program initiated by the Max Planck Society (MPG), managed jointly with the National Science Centre, and mutually funded by the Ministry of Science and Higher Education (MNiSW) and the German Federal Ministry of Education and Research (BMBF), and Sonata bis grant (2020/38/E/NZ4/00314) from National Science Centre.S

Targeting ERK3/MK5 complex for treatment of obesity and diabetes.

This dataset corresponds to the article titled “Targeting ERK3/MK5 complex for treatment of obesity and diabetes” published in Biochem Biophys Res Commun. 2022 Jul 5;612:119-125. doi: 10.1016/j.bbrc.2022.04.070. It comprises images of the original Western blots, along with the source data used for creating figures and conducting calculations. Further information related to this dataset can be found in the correspondingly titled article. This study was funded by European Research Council (ERC) Starting Grant SicMetabol (no.678119), Emmy Noether Grant Su820/1-1 from the German Research Foundation (DFG), EMBO Installation Grant from European Molecular Biology Organization (EMBO), the Dioscuri Centre of Scientific Excellence—The program initiated by the Max Planck Society (MPG), managed jointly with the National Science Centre, and mutually funded by the Ministry of Science and Higher Education (MNiSW) and the German Federal Ministry of Education and Research (BMBF), and Sonata bis grant (2020/38/E/NZ4/00314) from National Science Centre