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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

Authors

  • Mao B
  • Wu W
  • Li Y
  • Hoppe D
  • Stannek P
  • Glinka A
  • Niehrs C

Journal

Nature

Publication Data

May 17, 2001

Associated Grants

None

Mesh Terms

  • 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