Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Frizzled receptors are components of the Wnt signalling pathway, but how they activate the canonical Wnt/beta-catenin pathway is not clear. Here we use three distinct vertebrate frizzled receptors (Xfz3, Xfz4 and Xfz7) and describe whether and how their C-terminal cytoplasmic regions transduce the Wnt/beta-catenin signal. We show that Xfz3 activates this pathway in the absence of exogenous ligands, while Xfz4 and Xfz7 interact with Xwnt5A to activate this pathway. Analysis using chimeric receptors reveals that their C-terminal cytoplasmic regions are functionally equivalent in Wnt/beta-catenin signalling. Furthermore, a conserved motif (Lys-Thr-X-X-X-Trp) located two amino acids after the seventh transmembrane domain is required for activation of the Wnt/beta-catenin pathway and for membrane relocalization and phosphorylation of Dishevelled. Frizzled receptors with point mutations affecting either of the three conserved residues are defective in Wnt/beta-catenin signalling. These findings provide functional evidence supporting a role of this conserved motif in the modulation of Wnt signalling. They are consistent with the genetic features exhibited by Drosophila Dfz3 and Caenorhabditis elegans mom-5 in which the tryptophan is substituted by a tyrosine.
Adler,
The genetic control of tissue polarity in Drosophila.
1992, Pubmed
Adler,
The genetic control of tissue polarity in Drosophila.
1992,
Pubmed Axelrod,
Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways.
1998,
Pubmed
,
Xenbase Bassez,
Post-transcriptional regulation of ornithine decarboxylase in Xenopus laevis oocytes.
1990,
Pubmed
,
Xenbase Bhanot,
Frizzled and Dfrizzled-2 function as redundant receptors for Wingless during Drosophila embryonic development.
1999,
Pubmed Bhanot,
A new member of the frizzled family from Drosophila functions as a Wingless receptor.
1996,
Pubmed Bhat,
frizzled and frizzled 2 play a partially redundant role in wingless signaling and have similar requirements to wingless in neurogenesis.
1998,
Pubmed Boutros,
Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling.
1998,
Pubmed Boutros,
Signaling specificity by Frizzled receptors in Drosophila.
2000,
Pubmed
,
Xenbase Boutros,
Dishevelled: at the crossroads of divergent intracellular signaling pathways.
1999,
Pubmed
,
Xenbase 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 Carnac,
The homeobox gene Siamois is a target of the Wnt dorsalisation pathway and triggers organiser activity in the absence of mesoderm.
1996,
Pubmed
,
Xenbase Chen,
Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C.
2000,
Pubmed
,
Xenbase Cook,
Wingless inactivates glycogen synthase kinase-3 via an intracellular signalling pathway which involves a protein kinase C.
1996,
Pubmed Deardorff,
Frizzled-8 is expressed in the Spemann organizer and plays a role in early morphogenesis.
1998,
Pubmed
,
Xenbase Djiane,
Role of frizzled 7 in the regulation of convergent extension movements during gastrulation in Xenopus laevis.
2000,
Pubmed
,
Xenbase Du,
Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos.
1995,
Pubmed
,
Xenbase Fan,
Wnt signaling and transcriptional control of Siamois in Xenopus embryos.
1998,
Pubmed
,
Xenbase Gumbiner,
Carcinogenesis: a balance between beta-catenin and APC.
1997,
Pubmed Harland,
In situ hybridization: an improved whole-mount method for Xenopus embryos.
1991,
Pubmed
,
Xenbase He,
Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos.
1995,
Pubmed
,
Xenbase He,
A member of the Frizzled protein family mediating axis induction by Wnt-5A.
1997,
Pubmed
,
Xenbase Heasman,
Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos.
1994,
Pubmed
,
Xenbase Itoh,
A role for Xenopus Frizzled 8 in dorsal development.
1998,
Pubmed
,
Xenbase Kengaku,
Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud.
1998,
Pubmed Kennerdell,
Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway.
1998,
Pubmed Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed Krasnow,
A single frizzled protein has a dual function in tissue polarity.
1994,
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 McKendry,
LEF-1/TCF proteins mediate wnt-inducible transcription from the Xenopus nodal-related 3 promoter.
1997,
Pubmed
,
Xenbase Medina,
Xenopus frizzled 7 can act in canonical and non-canonical Wnt signaling pathways: implications on early patterning and morphogenesis.
2000,
Pubmed
,
Xenbase Miller,
Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways.
1999,
Pubmed Mlodzik,
Planar polarity in the Drosophila eye: a multifaceted view of signaling specificity and cross-talk.
1999,
Pubmed Moon,
WNTs modulate cell fate and behavior during vertebrate development.
1997,
Pubmed Moon,
From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus.
1998,
Pubmed
,
Xenbase Moon,
Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis.
1993,
Pubmed
,
Xenbase Moon,
In pursuit of the functions of the Wnt family of developmental regulators: insights from Xenopus laevis.
1993,
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 Morin,
Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC.
1997,
Pubmed Rocheleau,
Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos.
1997,
Pubmed Rothbächer,
Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis.
2000,
Pubmed
,
Xenbase Rubinfeld,
Stabilization of beta-catenin by genetic defects in melanoma cell lines.
1997,
Pubmed Rupp,
Xenopus embryos regulate the nuclear localization of XMyoD.
1994,
Pubmed
,
Xenbase Sasai,
Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes.
1994,
Pubmed
,
Xenbase Sato,
Dfrizzled-3, a new Drosophila Wnt receptor, acting as an attenuator of Wingless signaling in wingless hypomorphic mutants.
1999,
Pubmed Sawa,
The Caenorhabditis elegans gene lin-17, which is required for certain asymmetric cell divisions, encodes a putative seven-transmembrane protein similar to the Drosophila frizzled protein.
1996,
Pubmed Sheldahl,
Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner.
1999,
Pubmed
,
Xenbase Shi,
Xenopus frizzled 4 is a maternal mRNA and its zygotic expression is localized to the neuroectoderm and trunk lateral plate mesoderm.
2000,
Pubmed
,
Xenbase Shi,
Expression of Xfz3, a Xenopus frizzled family member, is restricted to the early nervous system.
1998,
Pubmed
,
Xenbase Slusarski,
Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling.
1997,
Pubmed
,
Xenbase Smith,
A nodal-related gene defines a physical and functional domain within the Spemann organizer.
1995,
Pubmed
,
Xenbase Sokol,
Analysis of Dishevelled signalling pathways during Xenopus development.
1996,
Pubmed
,
Xenbase Sokol,
Wnt signaling and dorso-ventral axis specification in vertebrates.
1999,
Pubmed Strutt,
The role of RhoA in tissue polarity and Frizzled signalling.
1997,
Pubmed Sumanas,
The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning.
2000,
Pubmed
,
Xenbase Tada,
Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway.
2000,
Pubmed
,
Xenbase Thorpe,
Wnt signaling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm.
1997,
Pubmed Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase Ungar,
Wnt4 affects morphogenesis when misexpressed in the zebrafish embryo.
1995,
Pubmed
,
Xenbase Wallingford,
Dishevelled controls cell polarity during Xenopus gastrulation.
2000,
Pubmed
,
Xenbase Wang,
A large family of putative transmembrane receptors homologous to the product of the Drosophila tissue polarity gene frizzled.
1996,
Pubmed Willert,
Casein kinase 2 associates with and phosphorylates dishevelled.
1997,
Pubmed Wodarz,
Mechanisms of Wnt signaling in development.
1998,
Pubmed
,
Xenbase Yanagawa,
The dishevelled protein is modified by wingless signaling in Drosophila.
1995,
Pubmed Yang-Snyder,
A frizzled homolog functions in a vertebrate Wnt signaling pathway.
1996,
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
