In an in vitro assay, expression of Dsh has been shown to induce phosphorylation of Jun, indicating that Dsh is a potent activator of the JNK pathway. The planar polarity-specific dsh1 allele is found to be mutated in the DEP domain. It is intriguing to speculate that a subset of Fz proteins might signal through a similar pathway. It was also shown recently that XWnt5A and rFz2, in a heterologous assay, increase intracellular calcium via G proteins and phosphoinositol signaling. A mutation in the beta-subunit of a heterotrimeric G protein in C. elegans prevents correct spindle orientation, a process that is believed to be dependent on a Wnt and a Fz receptor, but not on Arm.
All Dishevelled proteins have three highly conserved domains.
Sequence analysis reveals that Dsh has a PDZ domain. Many other signaling proteins contain PDZ domains that can bind to a conserved stretch of amino acids at the C-termini of receptors to form homotypic complexes with other PDZ domains. Multi-domain PDZ domain proteins have been proposed to integrate signaling molecules into larger complexes. It is not yet known whether DEP domains play an active role in regulating G proteins.