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The WNT/calcium pathway: biochemical mediators, tools and future requirements.

Wnt proteins represent a family of secreted, lipid-modified glycoproteins that can activate different intracellular pathways. Upon binding to certain members of the Frizzled family of Wnt receptors some Wnts like Wnt-4, Wnt-5A or Wnt-11 are able to elicit an intracellular release of calcium ions. This calcium signaling acitivity is sufficient to activate calcium sensitive enzymes like protein kinase C (PKC), calcium-calmodulin dependent kinase II (CamKII) or calcineurin (CaCN). This so-called Wnt/calcium pathway plays important roles during dorso-ventral patterning of the embryo, regulating cell migration, as well as heart development, and might play a role during tumor suppression. The foci of this review are the biochemical aspects of Wnt/calcium signaling, the tools that are available to study Wnt/calcium signaling, and the open questions that need to be addressed in the future to validate this signaling pathway.