Beta-arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways

EMBO Rep. 2008 Dec;9(12):1244-50. doi: 10.1038/embor.2008.193. Epub 2008 Oct 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Arrestins / metabolism*
  • Casein Kinase I / metabolism*
  • Casein Kinase II / metabolism*
  • Cell Line
  • Dishevelled Proteins
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Enzyme Activation
  • Gastrulation
  • Humans
  • Mice
  • Phosphoproteins / metabolism
  • Signal Transduction*
  • Wnt Proteins / metabolism*
  • Xenopus / embryology
  • Xenopus Proteins
  • beta-Arrestins
  • rac1 GTP-Binding Protein / metabolism


  • Adaptor Proteins, Signal Transducing
  • Arrestins
  • DVL1 protein, Xenopus
  • Dishevelled Proteins
  • Phosphoproteins
  • Wnt Proteins
  • Xenopus Proteins
  • beta-Arrestins
  • Casein Kinase I
  • Casein Kinase II
  • rac1 GTP-Binding Protein