Non-canonical pathway induced by Wnt3a regulates β-catenin via Pyk2 in differentiating human neural progenitor cells

Wnt/β-catenin and Wnt/Ca2+ pathways are involved in cellular processes during embryonic development and the interaction between them in the same cell decides the outcome of cellular functions. In this study, we showed that Wnt3a triggers the Wnt/Ca2+ signaling pathway, indicated by an increase of cytosolic free calcium ([Ca2+]i) and activation of calmodulin dependent kinase II (CaMKII) during the differentiation of human neuronal progenitor cells (hNPCs). Wnt3a via the increase of [Ca2+]i activates proline-rich tyrosine kinase 2 (Pyk2), which subsequently regulates phosphorylation of glycogen synthase kinase 3β (GSK3β) and β-catenin stabilization. Our findings suggest that Pyk2 plays an important role in the coordination of stabilization of β-catenin in the crosstalk between Wnt/β-catenin and Wnt/Ca2+ signaling pathways upon Wnt3a stimulation in differentiating hNPCs.