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1: Nature. 2001 May 17;411(6835):321-5.Click here to read Links
Comment in:
Nature. 2001 May 17;411(6835):255-6.

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

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

Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

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.

PMID: 11357136 [PubMed - indexed for MEDLINE]