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.
Pubmed ID: 11357136 RIS Download
Animals | Binding Sites | Cell Line | Cytoskeletal Proteins | Embryo, Nonmammalian | Embryonic Induction | Head | Humans | Intercellular Signaling Peptides and Proteins | Low Density Lipoprotein Receptor-Related Protein-1 | Low Density Lipoprotein Receptor-Related Protein-6 | 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