XB-ART-9855
Mol Cell Biol
2001 Jan 01;211:330-42. doi: 10.1128/MCB.21.1.330-342.2001.
Show Gene links
Show Anatomy links
Inhibition of the Wnt signaling pathway by Idax, a novel Dvl-binding protein.
???displayArticle.abstract???
In attempting to clarify the roles of Dvl in the Wnt signaling pathway, we identified a novel protein which binds to the PDZ domain of Dvl and named it Idax (for inhibition of the Dvl and Axin complex). Idax and Axin competed with each other for the binding to Dvl. Immunocytochemical analyses showed that Idax was localized to the same place as Dvl in cells and that expression of Axin inhibited the colocalization of Dvl and Idax. Further, Wnt-induced accumulation of beta-catenin and activation of T-cell factor in mammalian cells were suppressed by expression of Idax. Expression of Idax in Xenopus embryos induced ventralization with a reduction in the expression of siamois, a Wnt-inducible gene. Idax inhibited Wnt- and Dvl- but not beta-catenin-induced axis duplication. It is known that Dvl is a positive regulator in the Wnt signaling pathway and that the PDZ domain is important for this activity. Therefore, these results suggest that Idax functions as a negative regulator of the Wnt signaling pathway by directly binding to the PDZ domain of Dvl.
???displayArticle.pubmedLink??? 11113207
???displayArticle.pmcLink??? PMC88806
???displayArticle.link??? Mol Cell Biol
Species referenced: Xenopus
Genes referenced: ctnnb1 cxxc4 dvl1 dvl2 gsk3b sia1 wnt8a
References [+] :
Axelrod,
Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.
1998, Pubmed,
Xenbase
Axelrod, Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. 1998, Pubmed , Xenbase
Behrens, Functional interaction of beta-catenin with the transcription factor LEF-1. 1996, Pubmed , Xenbase
Behrens, Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. 1998, Pubmed , Xenbase
Boutros, Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling. 1998, Pubmed
Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. 1976, Pubmed
Brannon, A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. 1997, Pubmed , Xenbase
Cadigan, Wnt signaling: a common theme in animal development. 1997, Pubmed , Xenbase
Craven, PDZ proteins organize synaptic signaling pathways. 1998, Pubmed
Dale, Signal transduction by the Wnt family of ligands. 1998, Pubmed
Fagotto, Domains of axin involved in protein-protein interactions, Wnt pathway inhibition, and intracellular localization. 1999, Pubmed , Xenbase
Funayama, Embryonic axis induction by the armadillo repeat domain of beta-catenin: evidence for intracellular signaling. 1995, Pubmed , Xenbase
Hart, Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. 1998, Pubmed , Xenbase
Hart, The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. 1999, Pubmed
He, PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. 1999, Pubmed
He, Identification of c-MYC as a target of the APC pathway. 1998, Pubmed
Heisenberg, Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. 2000, Pubmed
Huber, Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. 1996, Pubmed , Xenbase
Huelsken, Requirement for beta-catenin in anterior-posterior axis formation in mice. 2000, Pubmed
Ikeda, Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. 1998, Pubmed
Ikeda, GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin. 2000, Pubmed
Itoh, Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction. 2000, Pubmed , Xenbase
Itoh, Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin. 1998, Pubmed , Xenbase
Kadoya, Inhibition of Wnt signaling pathway by a novel axin-binding protein. 2000, Pubmed , Xenbase
Kao, The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos. 1988, Pubmed , Xenbase
Kikuchi, Roles of Axin in the Wnt signalling pathway. 1999, Pubmed
Kishida, DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability. 1999, Pubmed
Kishida, Axin prevents Wnt-3a-induced accumulation of beta-catenin. 1999, Pubmed
Kishida, Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. 1998, Pubmed
Kitagawa, An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. 1999, Pubmed
Klingensmith, The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. 1994, Pubmed
Klingensmith, Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2. 1996, Pubmed , Xenbase
Korinek, Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. 1997, Pubmed
Kozak, An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. 1987, Pubmed
Krieg, Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. 1984, Pubmed , Xenbase
Lee, Characterization of mouse dishevelled (Dvl) proteins in Wnt/Wingless signaling pathway. 1999, Pubmed
Lemaire, Expression cloning of Siamois, a Xenopus homeobox gene expressed in dorsal-vegetal cells of blastulae and able to induce a complete secondary axis. 1995, Pubmed , Xenbase
Li, Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. 1999, Pubmed , Xenbase
Li, Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells. 1999, Pubmed
Liu, Requirement for Wnt3 in vertebrate axis formation. 1999, Pubmed
Mann, Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. 1999, Pubmed
Miller, Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. 1999, Pubmed
Molenaar, XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. 1996, Pubmed , Xenbase
Moon, From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. 1998, Pubmed , Xenbase
Moriguchi, Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates. 1999, Pubmed , Xenbase
Nakashima, Small G protein Ral and its downstream molecules regulate endocytosis of EGF and insulin receptors. 1999, Pubmed
Peters, Casein kinase I transduces Wnt signals. 1999, Pubmed , Xenbase
Pizzuti, cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene. 1996, Pubmed
Rothbächer, Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. 2000, Pubmed , Xenbase
Sakamoto, A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation. 2000, Pubmed , Xenbase
Sakanaka, Casein kinase iepsilon in the wnt pathway: regulation of beta-catenin function. 1999, Pubmed , Xenbase
Sakanaka, Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription. 1998, Pubmed
Scharf, Determination of the dorsal-ventral axis in eggs of Xenopus laevis: complete rescue of uv-impaired eggs by oblique orientation before first cleavage. 1980, Pubmed , Xenbase
Shibamoto, Cytoskeletal reorganization by soluble Wnt-3a protein signalling. 1998, Pubmed
Shtutman, The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. 1999, Pubmed
Smalley, Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription. 1999, Pubmed
Sokol, Analysis of Dishevelled signalling pathways during Xenopus development. 1996, Pubmed , Xenbase
Songyang, Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. 1997, Pubmed
Strovel, Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. 2000, Pubmed
Strutt, The role of RhoA in tissue polarity and Frizzled signalling. 1997, Pubmed
Sussman, Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled. 1994, Pubmed
Tada, Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. 2000, Pubmed , Xenbase
Takada, Wnt-3a regulates somite and tailbud formation in the mouse embryo. 1994, Pubmed
Tetsu, Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. 1999, Pubmed
Theisen, dishevelled is required during wingless signaling to establish both cell polarity and cell identity. 1994, Pubmed
Tian, Post-transcriptional regulation of Xwnt-8 expression is required for normal myogenesis during vertebrate embryonic development. 1999, Pubmed , Xenbase
van Genderen, Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. 1994, Pubmed
Willert, Casein kinase 2 associates with and phosphorylates dishevelled. 1997, Pubmed
Wodarz, Mechanisms of Wnt signaling in development. 1998, Pubmed , Xenbase
Yamamoto, Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. 1999, Pubmed
Yamamoto, Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3beta and beta-catenin and inhibits axis formation of Xenopus embryos. 1998, Pubmed , Xenbase
Yanagawa, The dishevelled protein is modified by wingless signaling in Drosophila. 1995, Pubmed
Yanagawa, Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant-negative Zeste-White 3 leads to elevated DE-cadherin in Drosophila clone 8 wing disc cells. 1997, Pubmed
Yost, GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis. 1998, Pubmed , Xenbase
Yost, The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. 1996, Pubmed , Xenbase
Zeng, The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. 1997, Pubmed , Xenbase