Extracellular-signal regulated kinase (Erk1/2), mitogen-activated protein kinase-activated protein kinase 2 (MK2) and tristetraprolin (TTP) comprehensively regulate injury-induced immediate early gene (IEG) response in in vitro liver organ culture

Summary of signal transduction pathways in the liver slices after injury. (A) After liver injury, p38MAPK (p38) and MK2 are activated within minutes from the edge of the cut as well as from the mesothelial sheet. At the same time, Erk1/2 kinase is similarly activated. Erk1/2 pathways induced a number of IEG genes that are required for cell cycle progression. MK2 mediated TTP degradation and enhanced IEG. (B) In MK2 -/- liver, Erk1/2 is activated but TTP is not ubiquitinated via MK2 activation, but accumulates and suppresses IEG response. Thus, the G1 to S phase transition is impaired.134