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西亚试剂:proteins repress canonical Wnt signaling via its interactio

NFAT proteins repress canonical Wnt signaling via its interaction with Dvl and participate in regulating neural progenitor cell proliferation and differentiation

Tao Huang, Zhihui Xie, Jiyong Wang, Meng Li, Naihe Jing and Lin Li

The Ca2+ signaling pathway appears to regulate the processes of the early development through its antagonism of canonical Wnt/β-catenin signaling pathway. However, the underlying mechanism is still poorly understood. Here, we show that NFAT, a component of Ca2+ signaling, directly interacts with Dvl in a Ca2+-dependent manner. A dominant-negative form of NFAT rescued the inhibition of the Wnt/β-catenin pathway triggered by Ca2+ signal. NFAT functioned downstream of β-catenin without interfering with its stability, but influencing the interaction of β-catenin with Dvl by its competitively binding to Dvl. Furthermore, we demonstrate that NFAT is a regulator in the proliferation and differentiation of neural progenitor cells by modulating canonical Wnt/β-catenin signaling pathway in the neural tube of chick embryo. Our findings suggest that NFAT negatively regulates canonical Wnt/β-catenin signaling by binding to Dvl, thereby participating in vertebrate neurogenesis.