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Titolo:
Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6
Autore:
Semenov, MV; Tamai, K; Brott, BK; Kuhl, M; Sokol, S; He, X;
Indirizzi:
Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol,Div Neurosci, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 eurol,Div Neurosci, Boston, MA 02115 USA Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Microbiol & MolGenet, Boston, MA 02215 USA Harvard Univ Boston MA USA 02215 crobiol & MolGenet, Boston, MA 02215 USA Univ Gottingen, Entwicklungsbiochem Jr Grp SFB 271, D-37073 Gottingen, Germany Univ Gottingen Gottingen Germany D-37073 271, D-37073 Gottingen, Germany
Titolo Testata:
CURRENT BIOLOGY
fascicolo: 12, volume: 11, anno: 2001,
pagine: 951 - 961
SICI:
0960-9822(20010626)11:12<951:HIDIAL>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONVERGENT EXTENSION MOVEMENTS; SPEMANN ORGANIZER; PRECHORDAL PLATE; SECRETED PROTEINS; BIOCHEMICAL-CHARACTERIZATION; TISSUE POLARITY; XENOPUS EMBRYOS; ZEBRAFISH DKK1; CELL POLARITY; ACTIVIN-A;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: He, X Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol,Div Neurosci, 300Longwood Ave, Boston, MA 02115 USA Harvard Univ 300 Longwood Ave Boston MAUSA 02115 ston, MA 02115 USA
Citazione:
M.V. Semenov et al., "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6", CURR BIOL, 11(12), 2001, pp. 951-961

Abstract

Background: Dickkopf-1 (Dkk-1) is a head inducer secreted from the vertebrate head organizer and induces anterior development by antagonizing Wnt signaling, Although several families of secreted antagonists have been shown to inhibit Wnt signal transduction by binding to Wnt, the molecular mechanism of Dkk-1 action is unknown. The Wnt family of secreted growth factors initiates signaling via the Frizzled (Fz) receptor and its candidate coreceptor, LDL receptor-related protein 6 (LRP6), presumably through Fz-LRP6 complex formation induced by Wnt. The significance of the Fz-LRP6 complex in signal transduction remains to be established. Results: We report that Dkk-1 is a high-affinity ligand for LRP6 and inhibits Wnt signaling by preventing Fz-LRP6 complex formation induced by Wnt. Dkk-1 binds neither Wnt nor Fz, nor does it affect Wnt-Fz interaction. Dkk-1function in head induction and Wnt signaling inhibition strictly correlates with its ability to bind LRP6 and to disrupt the Fz-LRP6 association. LRP6 function and Dkk-1 inhibition appear to be specific for the Wnt/Fz beta -catenin pathway. Conclusions: Our results demonstrate that Dkk-1 is an LRP6 ligand and inhibits Wnt signaling by blocking Wnt-induced Fz-LRP6 complex formation. Our findings thus reveal a novel mechanism for Wnt signal modulation. LRP6 is a Wnt coreceptor that appears to specify Wnt/Fz signaling to the beta -catenin pathway, and Dkk-1,distinct from Wnt binding antagonists, may be a specific inhibitor for Wnt/beta -catenin signaling. Our findings suggest that Wnt-Fz-LRP6 complex formation, but not Wnt-Fz interaction, triggers Wnt/beta -catenin signaling. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 10:43:39