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. 2016 Sep 21;7:12887. doi: 10.1038/ncomms12887

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Copyright © 2016, The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Signal inputs and outputs of the Wnt, Hh and Notch signals are coordinated intracellularly by parafibromin, which acts as a transcriptional platform/scaffold. Depending on its cellular context, parafibromin competitively interacts with β-catenin or Gli1, thereby activating Wnt and Hh signals in a mutually exclusive manner. On the other hand, parafibromin forms a heterotrimeric complex with β-catenin and Notch intracellular domain (NICD), supporting concerted activation of Wnt and Notch signals. This platform function of parafibromin is inversely regulated by parafibromin tyrosine phosphorylation and dephosphorylation, which are mediated by PTK6 and SHP2, respectively.