Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amino Acid Sequence
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Animals
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Axin Protein
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COS Cells
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Gene Expression / physiology
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Glycogen Synthase Kinase 3
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LDL-Receptor Related Proteins
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Low Density Lipoprotein Receptor-Related Protein-5
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Mammals
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Mice
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Molecular Sequence Data
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Mutagenesis / physiology
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Protein Binding / physiology
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Protein Structure, Tertiary
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Receptors, LDL / chemistry
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Receptors, LDL / genetics
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Receptors, LDL / metabolism*
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Repressor Proteins*
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Signal Transduction / physiology*
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Wnt Proteins
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Zebrafish Proteins*
Substances
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Axin Protein
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LDL-Receptor Related Proteins
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Low Density Lipoprotein Receptor-Related Protein-5
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Lrp5 protein, mouse
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Proteins
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Proto-Oncogene Proteins
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Receptors, LDL
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Repressor Proteins
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Wnt Proteins
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Zebrafish Proteins
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3