Further analysis of MK2/MK3 double knockout mice: p38 signaling, tumorigenesis and cell migration

• Antragsteller: Professor Dr. Matthias Gaestel
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2006 bis 2014
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 25966000

MAPK-activated protein kinase 2 (MK2) as a substrate of p38 is involved in diverse cellular activities, such as posttranscriptional regulation of cytokine expression, chromatin remodelling and cell cycle checkpoint control and, hence, is a potential target molecule for therapy of chronic inflammation or cancer. MK3, another target of p38, is highly homologous to MK2 protein. In our preliminary studies we performed extensive comparative analysis of both kinases in in vitro and in vivo experiments without identifying significant differences. Our aim is now to study MK3 function by phenotypic characterisation of recently produced MK3-deficient mice especially in inflammatory response and stress-induced cell cycle-arrest. To understand the biological significance of MK3 as well as the redundancy and compensation between MK2 and MK3, we further plan to produce and characterize MK2/3 double KO mouse strain in cytokine expression, cell cycle regulation and chromatin remodelling. Furthermore, we will continue to identify substrates of MK2 and MK3 by using different experimental approaches such as affinity purification and phosphor-proteomics and will apply a Ras-recruitment Y2H system to compare protein interaction and scaffolding for MK2 and MK3.

• DFG-Verfahren: Sachbeihilfen