Editors' ChoiceSignaling framework

Wnt cascade gains dishevelled kinase

Science's STKE  28 Sep 1999:
Vol. 1999, Issue 1, pp. tw3
DOI: 10.1126/stke.1999.1.tw3

Wnt is a secreted protein that binds to receptors of the Frizzled family. This interaction activates a signaling cascade that controls gene expression during cell growth and developmental processes. The known components of this cascade include the proteins dishevelled, glycogen synthase kinase-3, and β-catenin. Peters et al. reveal that in the developing frog and worm, a serine-threonine kinase called casein kinase I (CKI) functions in the Wnt signaling pathway. In Xenopus laevis, overexpression of CKI mimicked the effects of Wnt overexpression in producing a secondary dorsal axis, stabilizing β-catenin, and inducing the expression of Wnt-target genes. In Caenorhabditis elegans, inhibition of CKI produced the same mesoderm phenotype as loss of Wnt-signaling. The authors demonstrate that CKI is positioned downstream of dishevelled, and upstream of β-catenin. CKI also interacted with and phosphorylated dishevelled. It is possible that phosphorylation of dishevelled by CKI modulates downstream signaling events in the Wnt pathway.

Peters, J.M., McKay, R.M., McKay, J.P., and Graff, J.M. (1999) Casein kinase I transduces Wnt signals. Nature 401: 345-350. Online Journal