Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/β-catenin signalling

被引:172
作者
Wu, W
Glinka, A
Delius, H
Niehrs, C
机构
[1] Deutsch Krebsforschungszentrum, Div Mol Embryol, D-69120 Heidelberg, Germany
[2] Deutsch Krebsforschungszentrum, Div Appl Tumor Virol, D-69120 Heidelberg, Germany
关键词
D O I
10.1016/S0960-9822(00)00868-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Wnts are secreted glycoproteins implicated in diverse processes during embryonic patterning in metazoans. They signal through seven-transmembrane receptors of the Frizzled (Fz) family [1] to stabilise beta -catenin [2]. Wnts are antagonised by several extracellular inhibitors including the product of the dickkopf1 (dkk1) gene, which was identified in Xenopus embryos and is a member of a multigene family. The dkk1 gene acts upstream of the Wnt pathway component dishevelled but its mechanism of action is unknown [3]. Although the function of Dkk1 as a Wnt inhibitor in vertebrates is well established [3-6], the effect of other Dkks on the wnt/beta -catenin pathway is unclear. Here, we report that a related family member, Dkk2, activates rather than inhibits the wnt/beta -catenin signalling pathway in Xenopus embryos. Dkk2 strongly synergised with Wnt receptors of the Fz family to induce Wnt signalling responses. The study identifies Dkk2 as a secreted molecule that is able to activate wnt/beta -catenin signalling. The results suggest that a coordinated interplay between inhibiting dkk1 and activating dkk2 can modulate Fz signalling.
引用
收藏
页码:1611 / 1614
页数:4
相关论文
共 21 条
[1]   A new member of the frizzled family from Drosophila functions as a Wingless receptor [J].
Bhanot, P ;
Brink, M ;
Samos, CH ;
Hsieh, JC ;
Wang, YS ;
Macke, JP ;
Andrew, D ;
Nathans, J ;
Nusse, R .
NATURE, 1996, 382 (6588) :225-230
[2]   Activation of Siamois by the Wnt pathway [J].
Brannon, M ;
Kimelman, D .
DEVELOPMENTAL BIOLOGY, 1996, 180 (01) :344-347
[3]  
Carnac G, 1996, DEVELOPMENT, V122, P3055
[4]   INTERACTIONS BETWEEN XWNT-8 AND SPEMANN ORGANIZER SIGNALING PATHWAYS GENERATE DORSOVENTRAL PATTERN IN THE EMBRYONIC MESODERM OF XENOPUS [J].
CHRISTIAN, JL ;
MOON, RT .
GENES & DEVELOPMENT, 1993, 7 (01) :13-28
[5]  
Deardorff' MA, 1998, DEVELOPMENT, V125, P2687
[6]   ROLE OF GLYCOGEN-SYNTHASE KINASE 3-BETA AS A NEGATIVE REGULATOR OF DORSOVENTRAL AXIS FORMATION IN XENOPUS EMBRYOS [J].
DOMINGUEZ, I ;
ITOH, K ;
SOKOL, SY .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8498-8502
[7]   Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling [J].
Fedi, P ;
Bafico, A ;
Soria, AN ;
Burgess, WH ;
Miki, T ;
Bottaro, DP ;
Kraus, MH ;
Aaronson, SA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (27) :19465-19472
[8]   Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction [J].
Glinka, A ;
Wu, W ;
Delius, H ;
Monaghan, AP ;
Blumenstock, C ;
Niehrs, C .
NATURE, 1998, 391 (6665) :357-362
[9]   Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation [J].
Hashimoto, H ;
Itoh, M ;
Yamanaka, Y ;
Yamashita, S ;
Shimizu, T ;
Solnica-Krezel, L ;
Hibi, M ;
Hirano, T .
DEVELOPMENTAL BIOLOGY, 2000, 217 (01) :138-152
[10]   A member of the frizzled protein family mediating axis induction by Wnt-5A [J].
He, X ;
SaintJeannet, JP ;
Wang, YS ;
Nathans, J ;
Dawid, I ;
Varmus, H .
SCIENCE, 1997, 275 (5306) :1652-1654