The p38 signalling cascade (adapted from http://www.sabiosciences.com/). RNA-binding proteins mediate regulation of cytokine mRNA stability through p38/MK2 signalling. LPS activates p38 MAPK signalling in a variety of cells, leading to transcriptional activation of cytokine genes or enhanced mRNA stability and translation (highlighted areas). The fate of adenine- and uridine- (AU-) rich elements (ARE) mRNA is dependent on the presence of destabilizing and stabilizing mRNA-binding proteins. p38 MAPK activates MK2 in the nucleus, allowing for MK2 translocation to the cytoplasm. MK2 subsequently phosphorylates destabilizing mRNA-binding proteins such as TTP. This action prevents TTP from interacting with ARE cytokines. Simultaneously, activation of the p38 MAPK pathway results in translocation of HuR, a stabilizing RNA-binding protein, from the nucleus to the cytoplasm. Thus, upon p38/MK2 activation and phosphorylation of TTP, cytokine mRNA stability is enhanced, because TTP is no longer dictating mRNA triage and exonuclease decay.