MAPK (p38)

MAPK inhibits autophagy (by inhibiting ULK1) and promotes inflammation

We find that LPS triggers p38α mitogen-activated protein kinase (MAPK)-dependent phosphorylation of ULK1 in microglial cells.

This phosphorylation inhibited ULK1 kinase activity, preventing it from binding to the downstream effector ATG13, and reduced autophagy in microglia. Consistently, p38α MAPK activity is required for LPS-induced morphological changes and the production of IL-1β by primary microglia in vitro and in the brain, which correlates with the p38α MAPK-dependent inhibition of autophagy.

Furthermore, inhibition of ULK1 alone was sufficient to promote an inflammatory response in the absence of any overt inflammatory stimulation.