β‐Arrestin and casein kinase 1/2 define distinct branches of non‐canonical WNT signalling pathways

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Abstract
Recent advances in understanding β‐catenin‐independent WNT (non‐canonical) signalling suggest an increasing complexity, raising the question of how individual non‐canonical pathways are induced and regulated. Here, we examine whether intracellular signalling components such as β‐arrestin (β‐arr) and casein kinases 1 and 2 (CK1 and CK2) can contribute to determining signalling specificity in β‐catenin‐independent WNT signalling to the small GTPase RAC‐1. Our findings indicate that β‐arr is sufficient and required for WNT/RAC‐1 signalling, and that casein kinases act as a switch that prevents the activation of RAC‐1 and promotes other non‐canonical WNT pathways through the phosphorylation of dishevelled (DVL, xDSH in Xenopus). Thus, our results indicate that the balance between β‐arr and CK1/2 determines whether WNT/RAC‐1 or other non‐canonical WNT pathways are activated.