How LRP6 Inhibits GSK3β in Wnt Signaling
Author Information
Author(s): Piao Shunfu, Lee Sun-Hye, Kim Hyunjoon, Yum Soohwan, Stamos Jennifer L., Xu Yongbin, Lee Su-Jin, Lee Jaewon, Oh Sangtaek, Han Jin-Kwan, Park Bum-Joon, Weis William I., Ha Nam-Chul
Primary Institution: Pusan National University
Hypothesis
The intracellular region of LRP6 acts as a direct GSK3β inhibitor in Wnt/β-catenin signal propagation.
Conclusion
Phosphorylated LRP6 directly inhibits GSK3β, suggesting a novel mechanism for activating Wnt/β-catenin signaling.
Supporting Evidence
- Overexpression of LRP6's intracellular region impairs GSK3β activity.
- Synthetic peptides with the PPPSPxS motif inhibit GSK3β in vitro.
- Microinjection of phosphorylated peptides into Xenopus embryos enhances Wnt signaling.
- Phosphorylated LRP6 motifs directly inhibit GSK3β in vitro.
- Phosphorylation of LRP6 enhances its binding to GSK3β.
Takeaway
This study shows that a part of a protein called LRP6 can stop another protein, GSK3β, from working, which helps a signaling pathway that is important for development.
Methodology
The study involved constructing GFP-fusion proteins, transfecting them into cells, and analyzing their effects on GSK3β and β-catenin.
Limitations
The physiological relevance of the concentrations used in the experiments may not reflect in vivo conditions.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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