LDL-receptor-related protein 6 is a receptor for Dickkopf proteins.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print Cited Medium: Print ISSN: 0028-0836 (Print) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

Trans-Activators* ; Xenopus Proteins* ; Zebrafish Proteins*; Proteins/*metabolism ; Receptors, Immunologic/*metabolism ; Receptors, LDL/*metabolism; Adaptor Proteins, Signal Transducing ; Animals ; Binding Sites ; Cell Line ; Chemokines ; Cytoskeletal Proteins/genetics ; Cytoskeletal Proteins/metabolism ; Embryo, Nonmammalian/embryology ; Embryo, Nonmammalian/metabolism ; Embryonic Induction ; Head/embryology ; 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/antagonists & inhibitors ; Proteins/chemistry ; Proteins/genetics ; Proto-Oncogene Proteins/antagonists & inhibitors ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Receptors, Immunologic/antagonists & inhibitors ; Receptors, Immunologic/chemistry ; Receptors, Immunologic/genetics ; Receptors, LDL/antagonists & inhibitors ; Receptors, LDL/chemistry ; Receptors, LDL/genetics ; Recombinant Fusion Proteins/antagonists & inhibitors ; Recombinant Fusion Proteins/metabolism ; Sequence Deletion/genetics ; Signal Transduction ; Substrate Specificity ; Wnt Proteins ; Xenopus laevis/embryology ; beta Catenin

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.

Comment in: Nature. 2001 May 17;411(6835):255-6. (PMID: 11357114)

0 (Adaptor Proteins, Signal Transducing)
0 (CTNNB1 protein, Xenopus)
0 (CTNNB1 protein, human)
0 (Chemokines)
0 (Cytoskeletal Proteins)
0 (DKK1 protein, human)
0 (DKK2 protein, human)
0 (DKK3 protein, human)
0 (Dkk1 protein, mouse)
0 (Dkk2 protein, Xenopus)
0 (Dkk3 protein, Xenopus)
0 (FZD8 protein, Xenopus)
0 (Intercellular Signaling Peptides and Proteins)
0 (LRP6 protein, human)
0 (Low Density Lipoprotein Receptor-Related Protein-1)
0 (Low Density Lipoprotein Receptor-Related Protein-6)
0 (Lrp6 protein, mouse)
0 (Proteins)
0 (Proto-Oncogene Proteins)
0 (RNA, Messenger)
0 (Receptors, Cell Surface)
0 (Receptors, Immunologic)
0 (Receptors, LDL)
0 (Recombinant Fusion Proteins)
0 (Trans-Activators)
0 (Wnt Proteins)
0 (Xenopus Proteins)
0 (Zebrafish Proteins)
0 (beta Catenin)
0 (dkk1 protein, Xenopus)
0 (dkk1b protein, zebrafish)
0 (wnt8a protein, zebrafish)

Date Created: 20010518 Date Completed: 20010621 Latest Revision: 20220321

20231215

10.1038/35077108

11357136