Ca2+/calmodulin-dependent protein kinase II is stimulated by Wnt and frizzled homologs and promotes ventral cell fates in Xenopus

Wnt ligands working through Frizzled receptors have a differential ability to stimulate release of intracellular calcium (Ca2+) and activation of prot ein kinase C (PKC). Since targets of this Ca2+ release could play a role in Wnt signaling, we first tested the hypothesis that Ca2+/ calmodulin-depend ent protein kinase II (CamKII) is activated by some Wnt and Frizzled homolo gs. We report that Wnt and Frizzled homologs that activate Ca2+ release and PKC also activate CamKII activity in Xenopus embryos, while Wnt and Frizzl ed homologs that activate beta-catenin function do not. This activation occ urs within 10 min after receptor activation in a pertussis toxin-sensitive manner, concomitant with autophosphorylation of endogenous CamKII. Based on data that Wnt-5A and Wnt-11 are present maternally in Xenopus eggs, and ac tivate CamKII, we then tested the hypothesis that CamKII participates in ax is formation in the early embryo. Measurements of endogenous CamKII activit y from dorsal and ventral regions of embryos revealed elevated activity on the prospective ventral side, which was suppressed by a dominant negative X wnt-11. If this spatial bias in CamKII activity were involved in promoting ventral cell fate one might predict that elevating CamKII activity on the d orsal side would inhibit dorsal cell fates, while reducing CamKII activity on the ventral side would promote dorsal cell fates. Results obtained by ex pression of CamKII mutants were consistent with this prediction, revealing that CamKII contributes to a ventral cell fate.