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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5831
pubmed:dateCreated
2007-6-15
pubmed:abstractText
Multiple signaling pathways, including Wnt signaling, participate in animal development, stem cell biology, and human cancer. Although many components of the Wnt pathway have been identified, unresolved questions remain as to the mechanism by which Wnt binding to its receptors Frizzled and Low-density lipoprotein receptor-related protein 6 (LRP6) triggers downstream signaling events. With live imaging of vertebrate cells, we show that Wnt treatment quickly induces plasma membrane-associated LRP6 aggregates. LRP6 aggregates are phosphorylated and can be detergent-solubilized as ribosome-sized multiprotein complexes. Phospho-LRP6 aggregates contain Wnt-pathway components but no common vesicular traffic markers except caveolin. The scaffold protein Dishevelled (Dvl) is required for LRP6 phosphorylation and aggregation. We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Axin Protein, http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins, http://linkedlifedata.com/resource/pubmed/chemical/LRP6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein..., http://linkedlifedata.com/resource/pubmed/chemical/Lrp6 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein, http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin, http://linkedlifedata.com/resource/pubmed/chemical/dishevelled proteins, http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1095-9203
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
316
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1619-22
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:17569865-Adaptor Proteins, Signal Transducing, pubmed-meshheading:17569865-Animals, pubmed-meshheading:17569865-Axin Protein, pubmed-meshheading:17569865-Cell Line, pubmed-meshheading:17569865-Cell Line, Tumor, pubmed-meshheading:17569865-Cell Membrane, pubmed-meshheading:17569865-Centrifugation, Density Gradient, pubmed-meshheading:17569865-Cytoplasm, pubmed-meshheading:17569865-Drosophila, pubmed-meshheading:17569865-Glycogen Synthase Kinase 3, pubmed-meshheading:17569865-HeLa Cells, pubmed-meshheading:17569865-Humans, pubmed-meshheading:17569865-LDL-Receptor Related Proteins, pubmed-meshheading:17569865-Low Density Lipoprotein Receptor-Related Protein-6, pubmed-meshheading:17569865-Mice, pubmed-meshheading:17569865-Models, Biological, pubmed-meshheading:17569865-Phosphoproteins, pubmed-meshheading:17569865-Phosphorylation, pubmed-meshheading:17569865-Repressor Proteins, pubmed-meshheading:17569865-Signal Transduction, pubmed-meshheading:17569865-Transfection, pubmed-meshheading:17569865-Wnt Proteins, pubmed-meshheading:17569865-Wnt3 Protein, pubmed-meshheading:17569865-beta Catenin
pubmed:year
2007
pubmed:articleTitle
Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation.
pubmed:affiliation
Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't