WNT-dependent activation of DVL induces the activation of RAC and the formation of a RAC-DVL complex in HEK293 cells (Habas et al, 2003). Activation of RAC and stimulation of PCP/CE signaling depends on the DEP but not the DIX domain of DVL, consistent with earlier reports (Axelrod et al, 1998; Boutros et al, 1998, Habas et al, 2001, Habas et al, 2003). There are conflicting reports regarding the requirement for the DVL PDZ domain in the WNT-dependent activation of RAC (Habas et al, 2003; Cajanek et al, 2013). Activation of RAC almost certainly involves a RAC-specific GEF activity, potentially associated with DVL. In dopaminergic neurons, TIAM1 has been identified as the GEF for WNT5a- and DVL-dependent activation of RAC (Cajanek et al, 2013), however it is not clear whether this is generally true in other cell types and for other WNT ligands. In some cases, RAC activation correlates with activation of the downstream effector c-Jun N terminal kinase (JNK). This is thought to regulate reorganization of the cytoskeleton, however the mechanism of JNK activation is unknown. In other cases, JNK activation appears to be dispensable to the WNT response (Yamanaka et al, 2002; Habas et al, 2003; Rosso et al, 2005; reviewed in Heaseman and Ridley, 2008; Lai et al, 2009)
