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The mitogen-activated protein kinase (MAPK) pathways are a group of conserved intracellular signalling pathways present in most cells including neurons and glia. These pathways respond to a variety of stimuli including growth factors, cytokines and oxidative stress to generate appropriate cellular responses such as modulation of gene expression, cell proliferation, differentiation and survival as well as the stress response (Korhonen and Moilanen, 2014). The details of the cascades have been discussed elsewhere (Dickinson and Keyse, 2006; Korhonen and Moilanen, 2014) but usually follow a three-tier structure; an MAP3K activates an MAPK kinase (MAPKK), which in turn activates an MAPK, that can in turn regulate the activity of its cellular target by phosphorylation of specific amino acid residues. Three groups of MAPK have been identified; the extracellular signal-regulated kinases of which extracellular signal-regulated kinase (ERK)1/2 and ERK5 form two distinct classes, c-JUN N-terminal kinases (JNK1, JNK2 and JNK3), and the p38 kinases (p38 α, β, γ and δ) (Wancket et al., 2012). The ERK1/2 and ERK5 pathways respond to both mitotic and stress signals provided by growth factors, hormones and inflammatory cytokines. The other MAPK, p38 and JNK, are activated in response to growth factors, cytokines, viral proteins, lipopolysaccharides as well as cellular stress conditions. Collectively, the MAPK pathways play important roles in regulating cellular ageing, cell division, cell survival/apoptosis, neuronal activity, insulin signalling, inflammation and the immune response (Dickinson and Keyse, 2006; Korhonen and Moilanen, 2014).

A role for mitogen-activated protein kinase phosphatase 1 (MKP1) in neural cell development and survival