Mammalian sterile 20-like kinase 1/2 inhibit Wnt/{beta}-catenin signaling pathway by directly binding Casein kinase 1 epsilon

In this study, using the tandem affinity purification and mass spectrometry analysis, CK1ε was identified as a novel partner of MST1. Further analysis showed that the interaction between MST1 and CK1ε was mediated by their kinase domains and enhanced by the activation of MST1. To exclude the interference of the phosphorylated YAP/TAZ, the transduction from MST1 to YAP/TAZ was blocked using anti-WW45 shRNA. In the sh-WW45 cells, MST1 still inhibited the Wnt3A-induced phosphorylation of DVL2 and Wnt/β-catenin signaling by disturbing the interaction of DVL2 and CK1ε. And the growth-suppressive effect of MST1 in the presence of Wnt3A was effectively relieved by the downstream activation of Wnt/β-catenin pathway. Moreover, MST2, the close homolog of MST1, also displayed the similar function in suppressing the Wnt/β-catenin pathway. Therefore, our research here revealed that, in addition to the phosphorylated YAP/TAZ, the Hippo pathway can suppress the Wnt/β-catenin pathway directly through MST1/2.

Source: BJ Cell - November 4, 2013 Category: Biochemistry Authors: F Xu, Y Wang, J Chang, S Du, L Diao, N Jiang, H Wang, D Ma, J Zhang Tags: BJ Signal Source Type: research