Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Cell signalling

Fill in the Wnt gaps

Nature Reviews Molecular Cell Biology volume 7, page 82 (2006)Cite this article

In the absence of Wnt, the formation of a complex between β-catenin and the β-catenin-binding proteins, axin, adenomatous polyposis coli (APC) and glycogen-synthase kinase-3 (GSK3), results in the phosphorylation of β-catenin by GSK3 and in β-catenin degradation. When cells are exposed to Wnt, the frizzled receptor and the low-density lipoprotein (LDL)-receptor-related protein-6 (LRP6) receptor become activated and form a complex. Axin is recruited to this receptor complex and β-catenin translocates to the nucleus where it regulates gene expression. The binding of axin to LRP6 has been associated with the phosphorylation of LRP6, which indicates that protein kinases must be recruited to the receptor after activation by Wnt. Zeng et al. and Davidson et al. sought to identify these kinases.

Wnt induces phosphorylation of LRP6 on several clusters of Ser and Thr residues that have a central Pro-rich motif (PPPSP), so Zeng et al. first tested the PPPSP motif for phosphorylation activity. A combination of genetic and biochemical analysis revealed that GSK3 is a kinase that phosphorylates the Ser residue in this motif. These results indicate a dual role for GSK3 in Wnt signalling; GSK3 phosphorylates β-catenin, which mediates β-catenin degradation, but it also phosphorylates and activates LRP6.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

ORIGINAL RESEARCH PAPERS

  1. Davidson, G. et al. Casein kinase 1γ couples Wnt receptor activation to cytoplasmic signal transduction. Nature 438, 867–872 (2005)

    Article  CAS  Google Scholar 

  2. Zeng, X. et al. A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation. Nature 438, 873–877 (2005)

    Article  CAS  Google Scholar 

FURTHER READING

  1. Nusse, R. Cell biology: relays at the membrane. Nature 438, 747–749 (2005)

    Article  CAS  Google Scholar 

Download references

Authors
  1. Ekat Kritikou
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kritikou, E. Fill in the Wnt gaps. Nat Rev Mol Cell Biol 7, 82 (2006). https://doi.org/10.1038/nrm1853

Download citation

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/nrm1853

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing