Rac1 activates JNK pathway vai PAK-independent mechanisms involving binding and stimulation of MAP3K (MAP3K10 and MAP3K11)
MLK3 overexpression is sufficient to activate JNK po- tently without affecting the phosphorylating activity of MAPK or p38
MLK3 binds the GTP-binding proteins Cdc42 and Rac1 in vivo and that MLK3 mediates activation of MEKK-SEK-JNK kinase cascade by Rac1 and Cdc42
MLK2 (MAP3K10) and MLK3 (MAP3K11) interact with the activated (GTP-bound) forms of Rac and Cdc42, with a slight preference for Rac.
When expressed in fibroblasts, MLK2 co-localizes with active, dually phosphorylated JNK to punctate structures along microtubules.
MLK2 and MLK3 interact with members of the KIF3 family of kinesin superfamily motor proteins and with KAP3A, the putative targeting component of KIF3 motor complex
Rac1 coordinately activates p70S6K and JNK via MLK3 activation