Diverse Roles of JNK and MKK Pathways in the Brain

Figure 2

MKK4 and MKK7 have different functions in the developing brain. MKK4 and MKK7 both activate JNKs, which phosphorylate MT-associated proteins such as MAP1B and DCX. Activated MAP1B and DCX regulate neuronal migration and axon elongation in the developing brain. However, JNK activated by MKK4 regulates radial migration but not axon elongation, whereas JNK activated by MKK7 controls both radial migration and axon elongation. These differences between MKK7 and MKK4 functions also appear at the molecular level. The phosphorylation of MAP1B requires that JNK be activated by both MKK4 and MKK7. However, the phosphorylation of DCX requires JNK activation only by MKK7 and not by MKK4.