University of Dundee

"MK2-TNF-signaling comes full circle"

Event Date: 
Thursday, May 24, 2018 - 13:00 to 14:00
Event Location: 
CTIR Sir Kenneth and Lady Noreen Murray Seminar Room
Host: 
Professor Simon Arthur
Event Speaker: 
Professor Matthias Gaestel
Institution: 
Hannover Medical University
Event Type: 
Seminar
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Abstract
MK2 (p38MAPK-activated protein kinase 2) is essential for the biosynthesis of tumor necrosis factor (TNF) mainly operating by post-transcriptional regulation via the mRNA-binding protein tristetraprolin. Deletion of MK2 reduced serum TNF and protected against endotoxic shock, demonstrating a positive role of p38MAPK/MK2 in TNF signaling at the level of ligand generation. In addition to that, MK2 directly phosphorylates the TNF receptor interacting kinase RIPK1. This phosphorylation suppresses RIPK1 activity, thereby limiting downstream signaling of the TNF-receptor to apoptosis and necroptosis. These findings point to a more complex, double-edged role of MK2 in TNF signaling to timely coordinate onset and resolution of inflammation.