The conserved Wnt/wingless (Wg) signalling pathway controls many essential developmental processes. Consequently, it must be tightly regulated to ensure that development proceeds smoothly. On , Lee and colleagues reveal for the first time that homeodomain-interacting protein kinases (Hipks) positively regulate Wnt/Wg signalling. They report that the expression of hipk in developing Drosophila wings rescues the effects of Wg signal loss, while its overexpression in Drosophilacells promotes Wg signalling by stabilizing Armadillo, the Drosophilaβ-catenin homolog, which interacts with the transcription factor Tcf to promote target gene expression (in vertebrate cells, β-catenin interacts with Lef1 to achieve the same outcome). Furthermore, in Wg transcriptional assays, Hipk enhances Tcf/Armadillo-mediated gene expression in a kinase-dependent manner. Finally, the researchers show that, in vertebrate cells, Hipk2 promotes both β-catenin stabilization and Lef1/β-catenin-mediated gene expression. Together, these results suggest that the Hipks have a conserved role in promoting Wnt signalling that,somewhat surprisingly, involves Hipks acting in both the cytosol and the nucleus.
