LDL-receptor-related protein 6 is a receptor for Dickkopf proteins.
Wnt glycoproteins have been implicated in diverse processes during embryonic patterning in metazoa. They signal through frizzled-type seven-transmembrane-domain receptors to stabilize beta-catenin. Wnt signalling is antagonized by the extracellular Wnt inhibitor dickkopf1 (dkk1), which is a member of a multigene family. dkk1 was initially identified as a head inducer in ... Xenopus embryos but the mechanism by which it blocks Wnt signalling is unknown. LDL-receptor-related protein 6 (LRP6) is required during Wnt/beta-catenin signalling in Drosophila, Xenopus and mouse, possibly acting as a co-receptor for Wnt. Here we show that LRP6 (ref. 7) is a specific, high-affinity receptor for Dkk1 and Dkk2. Dkk1 blocks LRP6-mediated Wnt/beta-catenin signalling by interacting with domains that are distinct from those required for Wnt/Frizzled interaction. dkk1 and LRP6 interact antagonistically during embryonic head induction in Xenopus where LRP6 promotes the posteriorizing role of Wnt/beta-catenin signalling. Thus, DKKs inhibit Wnt co-receptor function, exemplifying the modulation of LRP signalling by antagonists.
Mesh Terms:
Animals, Binding Sites, Cell Line, Cytoskeletal Proteins, Embryo, Nonmammalian, Embryonic Induction, Head, Humans, Intercellular Signaling Peptides and Proteins, LDL-Receptor Related Protein 1, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins, RNA, Messenger, Receptors, Cell Surface, Receptors, Immunologic, Receptors, LDL, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, Substrate Specificity, Trans-Activators, Wnt Proteins, Xenopus Proteins, Xenopus laevis, Zebrafish Proteins, beta Catenin
Animals, Binding Sites, Cell Line, Cytoskeletal Proteins, Embryo, Nonmammalian, Embryonic Induction, Head, Humans, Intercellular Signaling Peptides and Proteins, LDL-Receptor Related Protein 1, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proteins, Proto-Oncogene Proteins, RNA, Messenger, Receptors, Cell Surface, Receptors, Immunologic, Receptors, LDL, Recombinant Fusion Proteins, Sequence Deletion, Signal Transduction, Substrate Specificity, Trans-Activators, Wnt Proteins, Xenopus Proteins, Xenopus laevis, Zebrafish Proteins, beta Catenin
Nature
Date: May. 17, 2001
PubMed ID: 11357136
View in: Pubmed Google Scholar
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