Wnt and calcium signaling: β-Catenin-independent pathways

Wnt signaling is a complex pathway in which β-catenin is typically viewed as a central mediator. However, within the past 15 years, at least three Wnt-mediated pathways have been proposed that function independent of β-catenin. One pathway involves activation of calcium/calmodulin-dependent kinase II (CamKII) and protein kinase C (PKC). Another includes recruitment of heterotrimeric GTP-binding proteins to activate phospholipase C (PLC) and phosphodiesterase (PDE). Lastly, a pathway similar to the planar cell polarity (PCP) pathway in Drosophila has been identified that activates the Jun-N-terminal kinase (JNK) and, perhaps, small GTP-binding proteins. Calcium has been implicated as an important second messenger in all of these pathways. This review will focus on the role of calcium in Wnt signaling and, as a consequence, provide a limited overview of β-catenin-independent Wnt signaling.