| First Author | Wang K | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 34 | Pages | 23371-5 |
| PubMed ID | 18502762 | Mgi Jnum | J:140268 |
| Mgi Id | MGI:3813186 | Doi | 10.1074/jbc.M802376200 |
| Citation | Wang K, et al. (2008) Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. J Biol Chem 283(34):23371-5 |
| abstractText | Wnt signaling is involved in a wide range of developmental, physiological, and pathophysiological processes and is negatively regulated by Dickkopf1 (Dkk1). Dkk1 has been shown to bind to two transmembrane proteins, the low density lipoprotein receptor-related proteins (LRP) 5/6 and Kremen. Here, we show that Dkk1 residues Arg(197), Ser(198), and Lys(232) are specifically involved in its binding to Kremen rather than to LRP6. These residues are localized at a surface that is at the opposite side of the LRP6-binding surface based on a three-dimensional structure of Dkk1 deduced from that of Dkk2. We were surprised to find that the Dkk1 mutants carrying a mutation at Arg(197), Ser(198), or Lys(232), the key Kremen-binding residues, could antagonize Wnt signaling as well as the wild-type Dkk1. These mutations only affected their ability to antagonize Wnt signaling when both LRP6 and Kremen were coexpressed. These results suggest that Kremen may not be essential for Dkk1-mediated Wnt antagonism and that Kremen may only play a role when cells express a high level of LRP5/6. |
