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Wnt proteins synergize to activate β-catenin signaling.

Authors
  • Alok, Anshula1
  • Lei, Zhengdeng1, 2
  • Jagannathan, N Suhas1, 2
  • Kaur, Simran1
  • Harmston, Nathan2
  • Rozen, Steven G1, 2
  • Tucker-Kellogg, Lisa1, 2
  • Virshup, David M3, 4
  • 1 Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore. , (Singapore)
  • 2 Centre for Computational Biology, Duke-NUS Medical School, 169857 Singapore. , (Singapore)
  • 3 Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, 169857 Singapore [email protected] , (Singapore)
  • 4 Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
May 01, 2017
Volume
130
Issue
9
Pages
1532–1544
Identifiers
DOI: 10.1242/jcs.198093
PMID: 28289266
Source
Medline
Keywords
License
Unknown

Abstract

Wnt ligands are involved in diverse signaling pathways that are active during development, maintenance of tissue homeostasis and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. Here, we studied the effect of co-expression of Wnts on the β-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate β-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate β-catenin signaling in multiple cell types. WNT1- and WNT7B-mediated synergistic Wnt signaling requires FZD5, FZD8 and LRP6, as well as the WNT7B co-receptors GPR124 (also known as ADGRA2) and RECK. Unexpectedly, this synergistic signaling occurs downstream of β-catenin stabilization, and is correlated with increased lysine acetylation of β-catenin. Wnt synergy provides a general mechanism to confer increased combinatorial control over this important regulatory pathway.

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