Low-Density Lipoprotein Receptor-Related Protein-5 Binds to Axin and Regulates the Canonical Wnt Signaling Pathway
pmid: 11336703
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.
- University of Rochester United States
- University of Mary United States
- Medical Research Council United Kingdom
- Setsunan University Japan
- University of Connecticut United States
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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