Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway
Copyright policy )Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway
To understand how the Wnt coreceptor LRP-5 is involved in transducing the canonical Wnt signals, we identified Axin as a protein that interacts with the intracellular domain of LRP-5. LRP-5, when expressed in fibroblast cells, showed no effect on the canonical Wnt signaling pathway by itself, but acted synergistically with Wnt. In contrast, LRP-5 mutants lacking the extracellular domain functioned as constitutively active forms that bind Axin and that induce LEF-1 activation by destabilizing Axin and stabilizing beta-catenin. Addition of Wnt caused the translocation of Axin to the membrane and enhanced the interaction between Axin and LRP-5. In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway.
- Medical Research Council United Kingdom
- Chinese Academy of Sciences China (People's Republic of)
- University of Mary United States
- Shanghai Institutes for Biological Sciences China (People's Republic of)
- MRC Laboratory of Molecular Biology United Kingdom
Mammals, Molecular Sequence Data, Gene Expression, Proteins, Cell Biology, 3T3 Cells, Protein Structure, Tertiary, Repressor Proteins, Glycogen Synthase Kinase 3, Mice, Low Density Lipoprotein Receptor-Related Protein-5, Axin Protein, Receptors, LDL, Mutagenesis, Proto-Oncogene Proteins, COS Cells, Calcium-Calmodulin-Dependent Protein Kinases, Animals, Amino Acid Sequence, Molecular Biology, LDL-Receptor Related Proteins, Protein Binding
Mammals, Molecular Sequence Data, Gene Expression, Proteins, Cell Biology, 3T3 Cells, Protein Structure, Tertiary, Repressor Proteins, Glycogen Synthase Kinase 3, Mice, Low Density Lipoprotein Receptor-Related Protein-5, Axin Protein, Receptors, LDL, Mutagenesis, Proto-Oncogene Proteins, COS Cells, Calcium-Calmodulin-Dependent Protein Kinases, Animals, Amino Acid Sequence, Molecular Biology, LDL-Receptor Related Proteins, Protein Binding
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