Wnt signaling regulates embryo development and tissue homeostasis, and its deregulation leads to an array of diseases, including cancer. Dapper1 has been shown to be a key negative regulator of Wnt signaling. However, its function and regulation remain poorly understood. In this study, we report that 14-3-3β interacts with human Dapper1 (hDpr1). The interaction is dependent on protein kinase A (PKA)-mediated phosphorylation of hDpr1 at Ser-237 and Ser-827.14-3-3β binding attenuates the ability of hDpr1 to promote Dishevelled (Dvl) degradation, thus enhancing Wnt signaling. We further provide evidence that PKA-mediated Dpr1 phosphorylation may contribute to growth and tumor formation of colon cancer Caco2 cells. Finally, we show that cyclooxygenase-2 expression and PKA activation are positively correlated with Dvl protein levels in colon cancer samples. Together, our findings establish a novel layer of regulation of Wnt signaling by PKA via the 14-3-3-Dpr1-Dvl axis. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
CITATION STYLE
Chen, H., Liu, L., Ma, B., Ma, T. M., Hou, J. J., Xie, G. M., … Chen, Y. G. (2011). Protein kinase A-mediated 14-3-3 association impedes human Dapper1 to promote Dishevelled degradation. Journal of Biological Chemistry, 286(17), 14870–14880. https://doi.org/10.1074/jbc.M110.211607
Mendeley helps you to discover research relevant for your work.