*5.2.2 Mitogen-activated protein kinase (MAPK) family proteins*

In the distal stump of the peripheral nerve after injury SCs respond by activating MAPK proteins like extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (JNK), and p38 MAP kinase [66, 90–95].

**Ras/Raf/Erk** signaling in SC dedifferentiation was studied for the first time by Harrisingh et al., and they showed that the Raf activation suppresses the differentiation of primary SCs induced by cyclic adenosine monophosphate (cAMP) [91]. Raf is an activator of Erk. The authors demonstrated that the activation of Ras/Raf/ Erk pathway induced demyelination in an *in vitro* study on cocultured cells—SCs and neurons from dorsal root ganglia.

Erk activation is a pro-myelinating factor, and if Erk is inhibited, the SC differentiation and myelination are blocked, showed many *in vivo* studies [96–98].

In conclusion, Erk signaling is required in differentiation (Erk low levels) but also in dedifferentiation (high Erk levels) of SCs after nerve lesion [99, 100].

*JNK*, another MAPK protein, is implied in SC functions, so when c-Jun is activated by JNK, the migration and proliferation of SCs are produced [19, 101, 102].

Without insisting, we would like just to remember other MAPK proteins and signaling pathways involved in SC plasticity: **p38MAPK**, **PI3K/Akt/mTOR** signaling (reviewed by [42]).
