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EMBO Rep
2008 Dec 01;912:1244-50. doi: 10.1038/embor.2008.193.
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Beta-arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways.
Bryja V
,
Schambony A
,
Cajánek L
,
Dominguez I
,
Arenas E
,
Schulte G
.
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Recent advances in understanding beta-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 beta-arrestin (beta-arr) and casein kinases 1 and 2 (CK1 and CK2) can contribute to determining signalling specificity in beta-catenin-independent WNT signalling to the small GTPase RAC-1. Our findings indicate that beta-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 beta-arr and CK1/2 determines whether WNT/RAC-1 or other non-canonical WNT pathways are activated.
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