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Wnt proteins synergize to activate β-catenin signaling.

Publication ,  Journal Article
Alok, A; Lei, Z; Jagannathan, NS; Kaur, S; Harmston, N; Rozen, SG; Tucker-Kellogg, L; Virshup, DM
Published in: J Cell Sci
May 1, 2017

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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Published In

J Cell Sci

DOI

EISSN

1477-9137

Publication Date

May 1, 2017

Volume

130

Issue

9

Start / End Page

1532 / 1544

Location

England

Related Subject Headings

  • beta Catenin
  • Wnt Proteins
  • Up-Regulation
  • Stomach Neoplasms
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Protein Stability
  • Phosphorylation
  • Models, Biological
  • Low Density Lipoprotein Receptor-Related Protein-6
 

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Alok, A., Lei, Z., Jagannathan, N. S., Kaur, S., Harmston, N., Rozen, S. G., … Virshup, D. M. (2017). Wnt proteins synergize to activate β-catenin signaling. J Cell Sci, 130(9), 1532–1544. https://doi.org/10.1242/jcs.198093
Alok, Anshula, Zhengdeng Lei, N Suhas Jagannathan, Simran Kaur, Nathan Harmston, Steven G. Rozen, Lisa Tucker-Kellogg, and David M. Virshup. “Wnt proteins synergize to activate β-catenin signaling.J Cell Sci 130, no. 9 (May 1, 2017): 1532–44. https://doi.org/10.1242/jcs.198093.
Alok A, Lei Z, Jagannathan NS, Kaur S, Harmston N, Rozen SG, et al. Wnt proteins synergize to activate β-catenin signaling. J Cell Sci. 2017 May 1;130(9):1532–44.
Alok, Anshula, et al. “Wnt proteins synergize to activate β-catenin signaling.J Cell Sci, vol. 130, no. 9, May 2017, pp. 1532–44. Pubmed, doi:10.1242/jcs.198093.
Alok A, Lei Z, Jagannathan NS, Kaur S, Harmston N, Rozen SG, Tucker-Kellogg L, Virshup DM. Wnt proteins synergize to activate β-catenin signaling. J Cell Sci. 2017 May 1;130(9):1532–1544.
Journal cover image

Published In

J Cell Sci

DOI

EISSN

1477-9137

Publication Date

May 1, 2017

Volume

130

Issue

9

Start / End Page

1532 / 1544

Location

England

Related Subject Headings

  • beta Catenin
  • Wnt Proteins
  • Up-Regulation
  • Stomach Neoplasms
  • Signal Transduction
  • Receptors, G-Protein-Coupled
  • Protein Stability
  • Phosphorylation
  • Models, Biological
  • Low Density Lipoprotein Receptor-Related Protein-6