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PMID:11029007
| Citation |
Tamai, K, Semenov, M, Kato, Y, Spokony, R, Liu, C, Katsuyama, Y, Hess, F, Saint-Jeannet, JP and He, X (2000) LDL-receptor-related proteins in Wnt signal transduction. Nature 407:530-5 |
|---|---|
| Abstract |
The Wnt family of secreted signalling molecules are essential in embryo development and tumour formation. The Frizzled (Fz) family of serpentine receptors function as Wnt receptors, but how Fz proteins transduce signalling is not understood. In Drosophila, arrow phenocopies the wingless (DWnt-1) phenotype, and encodes a transmembrane protein that is homologous to two members of the mammalian low-density lipoprotein receptor (LDLR)-related protein (LRP) family, LRP5 and LRP6 (refs 12-15). Here we report that LRP6 functions as a co-receptor for Wnt signal transduction. In Xenopus embryos, LRP6 activated Wnt-Fz signalling, and induced Wnt responsive genes, dorsal axis duplication and neural crest formation. An LRP6 mutant lacking the carboxyl intracellular domain blocked signalling by Wnt or Wnt-Fz, but not by Dishevelled or beta-catenin, and inhibited neural crest development. The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex. |
| Links |
PubMed Online version:10.1038/35035117 |
| Keywords |
Animals; Cloning, Molecular; Drosophila Proteins; Frizzled Receptors; Humans; Low Density Lipoprotein Receptor-Related Protein-6; Membrane Proteins/metabolism; Mice; Molecular Sequence Data; Neural Crest/metabolism; Proto-Oncogene Proteins/metabolism; Receptors, G-Protein-Coupled; Receptors, LDL/metabolism; Recombinant Fusion Proteins; Signal Transduction; Wnt Proteins; Wnt1 Protein; Xenopus; Xenopus Proteins; Zebrafish Proteins |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
HUMAN:LRP6 |
part_of |
GO:1990851: Wnt-Frizzled-LRP5/6 complex |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q61091 |
C |
Seeded From UniProt |
complete | |
|
HUMAN:LRP6 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P04426 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:LRP6 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q61091 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:LRP6 |
involved_in |
GO:0014033: neural crest cell differentiation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:LRP6 |
involved_in |
GO:0014029: neural crest formation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:LRP6 |
enables |
GO:0017147: Wnt-protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P04426 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:LRP6 |
enables |
GO:0005109: frizzled binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:Q61091 |
F |
Seeded From UniProt |
complete | |
|
HUMAN:LRP6 |
involved_in |
GO:0060070: canonical Wnt signaling pathway |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
HUMAN:LRP6 |
enables |
GO:0071936: coreceptor activity involved in Wnt signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
HUMAN:LRP6 |
involved_in |
GO:0044335: canonical Wnt signaling pathway involved in neural crest cell differentiation |
ECO:0000305: curator inference used in manual assertion |
GO:0014033 |
P |
Seeded From UniProt |
complete | |
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O75581 |
F |
Seeded From UniProt |
complete | ||
|
XENLA:WNT3A |
involved_in |
GO:0014033: neural crest cell differentiation |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
XENLA:WNT5A |
involved_in |
GO:0060070: canonical Wnt signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O75581 |
F |
Seeded From UniProt |
complete | ||
|
involved_in |
GO:0060070: canonical Wnt signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0060070: canonical Wnt signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0005102: signaling receptor binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O75581 |
F |
Seeded From UniProt |
complete | ||
|
part_of |
GO:1990851: Wnt-Frizzled-LRP5/6 complex |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O75581 |
C |
Seeded From UniProt |
complete | ||
See also
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