Wnt Isoform-Specific Interactions with Coreceptor Specify Inhibition or Potentiation of Signaling by LRP6 Antibodies

Gong, Y., et al., 5(9), e12682, PLoS ONE, 2010

Several components of Wnt signaling are implicated in the genesis of human cancer. Wnt signaling includes numerous ligands, receptors and transcriptional effectors. Beta-catenin-dependent Wnt signaling is initiated as Wnt binds to both the receptor FZD and coreceptor LRP5/6, which then assembles a multimeric complex at the cytoplasmic membrane face to recruit and inactivate the kinase GSK3. The authors generated monoclonal antibodies against LRP6 with the unexpected ability to inhibit signaling by some Wnt isoforms and potentiate signaling by other isoforms. Their study results indicate that separate binding sites for different subsets of Wnt isoforms determine the inhibition or potentiation of signaling conferred by LRP6 antibodies. The LRP6 protein binding assays were performed on the Octet RED platform using Streptavidin biosensors loaded with biotinylated, HIS-tagged LRP6 proteins.

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