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???
Wnt pathways play essential roles in cell proliferation, morphogenesis, and cell fate specification during embryonic development. According to the consensus view, the Wnt pathway prevents the degradation of the key signaling component β-catenin by the protein complex containing the negative regulators Axin and glycogen synthase kinase 3 (GSK3). Stabilized β-catenin associates with TCF proteins and enters the nucleus to promote target gene expression. This study examines the involvement of HIPK2 (homeodomain-interacting protein kinase 2) in the regulation of different TCF proteins in Xenopus embryos in vivo. We show that the TCF family members LEF1, TCF4, and TCF3 are phosphorylated in embryonic ectoderm after Wnt8 stimulation and HIPK2 overexpression. We also find that TCF3 phosphorylation is triggered by canonical Wnt ligands, LRP6, and dominant negative mutants for Axin and GSK3, indicating that this process shares the same upstream regulators with β-catenin stabilization. HIPK2-dependent phosphorylation caused the dissociation of LEF1, TCF4, and TCF3 from a target promoter in vivo. This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling; HIPK2 up-regulates transcription by phosphorylating TCF3, a transcriptional repressor, but inhibits transcription by phosphorylating LEF1, a transcriptional activator. Finally, we show that upon HIPK2-mediated phosphorylation, TCF3 is replaced with positively acting TCF1 at a target promoter. These observations emphasize a critical role for Wnt/HIPK2-dependent TCF phosphorylation and suggest that TCF switching is an important mechanism of Wnt target gene activation in vertebrate embryos.
Arce,
Diversity of LEF/TCF action in development and disease.
2006, Pubmed
Arce,
Diversity of LEF/TCF action in development and disease.
2006,
Pubmed
Behrens,
Functional interaction of beta-catenin with the transcription factor LEF-1.
1996,
Pubmed
,
Xenbase
Blythe,
Chromatin immunoprecipitation in early Xenopus laevis embryos.
2009,
Pubmed
,
Xenbase
Boussif,
A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine.
1995,
Pubmed
Brunner,
pangolin encodes a Lef-1 homologue that acts downstream of Armadillo to transduce the Wingless signal in Drosophila.
1997,
Pubmed
Candia,
Cellular interpretation of multiple TGF-beta signals: intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads.
1997,
Pubmed
,
Xenbase
Cavallo,
Drosophila Tcf and Groucho interact to repress Wingless signalling activity.
1998,
Pubmed
Choi,
Phosphorylation by the DHIPK2 protein kinase modulates the corepressor activity of Groucho.
2005,
Pubmed
Christian,
Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis.
1991,
Pubmed
,
Xenbase
Clevers,
Wnt/beta-catenin signaling in development and disease.
2006,
Pubmed
Daniels,
Beta-catenin directly displaces Groucho/TLE repressors from Tcf/Lef in Wnt-mediated transcription activation.
2005,
Pubmed
Dauth,
Homeodomain-interacting protein kinase 2 is the ionizing radiation-activated p53 serine 46 kinase and is regulated by ATM.
2007,
Pubmed
Davidson,
Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction.
2005,
Pubmed
,
Xenbase
Dominguez,
Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos.
1995,
Pubmed
,
Xenbase
D'Orazi,
Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis.
2002,
Pubmed
Dorsky,
Two tcf3 genes cooperate to pattern the zebrafish brain.
2003,
Pubmed
Doxakis,
Homeodomain-interacting protein kinase-2 regulates apoptosis in developing sensory and sympathetic neurons.
2004,
Pubmed
Du,
Identification of distinct classes and functional domains of Wnts through expression of wild-type and chimeric proteins in Xenopus embryos.
1995,
Pubmed
,
Xenbase
Erter,
Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.
2001,
Pubmed
,
Xenbase
Galceran,
Wnt3a-/--like phenotype and limb deficiency in Lef1(-/-)Tcf1(-/-) mice.
1999,
Pubmed
Gawantka,
Antagonizing the Spemann organizer: role of the homeobox gene Xvent-1.
1995,
Pubmed
,
Xenbase
Grigoryan,
Deciphering the function of canonical Wnt signals in development and disease: conditional loss- and gain-of-function mutations of beta-catenin in mice.
2008,
Pubmed
Hata,
OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways.
2000,
Pubmed
,
Xenbase
Heasman,
Beta-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach.
2000,
Pubmed
,
Xenbase
Hikasa,
Regulation of TCF3 by Wnt-dependent phosphorylation during vertebrate axis specification.
2010,
Pubmed
,
Xenbase
Hikasa,
The involvement of Frodo in TCF-dependent signaling and neural tissue development.
2004,
Pubmed
,
Xenbase
Hikasa,
The Xenopus receptor tyrosine kinase Xror2 modulates morphogenetic movements of the axial mesoderm and neuroectoderm via Wnt signaling.
2002,
Pubmed
,
Xenbase
Hofmann,
HIPK2 regulates transforming growth factor-beta-induced c-Jun NH(2)-terminal kinase activation and apoptosis in human hepatoma cells.
2003,
Pubmed
Hofmann,
Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2.
2002,
Pubmed
Hoppler,
Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos.
1996,
Pubmed
,
Xenbase
Houston,
Repression of organizer genes in dorsal and ventral Xenopus cells mediated by maternal XTcf3.
2002,
Pubmed
,
Xenbase
Imai,
The homeobox genes vox and vent are redundant repressors of dorsal fates in zebrafish.
2001,
Pubmed
,
Xenbase
Ishitani,
Regulation of lymphoid enhancer factor 1/T-cell factor by mitogen-activated protein kinase-related Nemo-like kinase-dependent phosphorylation in Wnt/beta-catenin signaling.
2003,
Pubmed
Ishitani,
The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF.
1999,
Pubmed
,
Xenbase
Ishitani,
The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin signaling.
2003,
Pubmed
Isono,
Overlapping roles for homeodomain-interacting protein kinases hipk1 and hipk2 in the mediation of cell growth in response to morphogenetic and genotoxic signals.
2006,
Pubmed
Itoh,
Nuclear localization is required for Dishevelled function in Wnt/beta-catenin signaling.
2005,
Pubmed
,
Xenbase
Itoh,
A role for Xenopus Frizzled 8 in dorsal development.
1998,
Pubmed
,
Xenbase
Kaletta,
Binary specification of the embryonic lineage in Caenorhabditis elegans.
1997,
Pubmed
Kanei-Ishii,
Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK.
2004,
Pubmed
Karaulanov,
Transcriptional regulation of BMP4 synexpression in transgenic Xenopus.
2004,
Pubmed
,
Xenbase
Kim,
Repressor activity of Headless/Tcf3 is essential for vertebrate head formation.
2000,
Pubmed
Kim,
Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation.
2010,
Pubmed
,
Xenbase
Kim,
Ryk cooperates with Frizzled 7 to promote Wnt11-mediated endocytosis and is essential for Xenopus laevis convergent extension movements.
2008,
Pubmed
,
Xenbase
Kim,
Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors.
1998,
Pubmed
Kondo,
Characterization of cells and gene-targeted mice deficient for the p53-binding kinase homeodomain-interacting protein kinase 1 (HIPK1).
2003,
Pubmed
Ladher,
Xom: a Xenopus homeobox gene that mediates the early effects of BMP-4.
1996,
Pubmed
,
Xenbase
Lee,
Homeodomain-interacting protein kinases (Hipks) promote Wnt/Wg signaling through stabilization of beta-catenin/Arm and stimulation of target gene expression.
2009,
Pubmed
Lee,
Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.
2001,
Pubmed
,
Xenbase
Lin,
pop-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos.
1995,
Pubmed
Liu,
Distinct roles for Xenopus Tcf/Lef genes in mediating specific responses to Wnt/beta-catenin signalling in mesoderm development.
2005,
Pubmed
,
Xenbase
Liu,
beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation.
1999,
Pubmed
,
Xenbase
Lo,
Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans.
2004,
Pubmed
Logan,
The Wnt signaling pathway in development and disease.
2004,
Pubmed
Louie,
Modulation of the beta-catenin signaling pathway by the dishevelled-associated protein Hipk1.
2009,
Pubmed
,
Xenbase
MacDonald,
Wnt/beta-catenin signaling: components, mechanisms, and diseases.
2009,
Pubmed
,
Xenbase
Meneghini,
MAP kinase and Wnt pathways converge to downregulate an HMG-domain repressor in Caenorhabditis elegans.
1999,
Pubmed
Molenaar,
XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos.
1996,
Pubmed
,
Xenbase
Onichtchouk,
The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controlling [correction of controling] dorsoventral patterning of Xenopus mesoderm.
1996,
Pubmed
,
Xenbase
Ossipova,
PAR-1 phosphorylates Mind bomb to promote vertebrate neurogenesis.
2009,
Pubmed
,
Xenbase
Park,
Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals.
2006,
Pubmed
,
Xenbase
Peng,
Xenopus laevis: Practical uses in cell and molecular biology. Solutions and protocols.
1991,
Pubmed
,
Xenbase
Peters,
Casein kinase I transduces Wnt signals.
1999,
Pubmed
,
Xenbase
Phillips,
A new look at TCF and beta-catenin through the lens of a divergent C. elegans Wnt pathway.
2009,
Pubmed
Piao,
Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.
2008,
Pubmed
,
Xenbase
Pierantoni,
The homeodomain-interacting protein kinase 2 gene is expressed late in embryogenesis and preferentially in retina, muscle, and neural tissues.
2002,
Pubmed
Price,
CKI, there's more than one: casein kinase I family members in Wnt and Hedgehog signaling.
2006,
Pubmed
Pukrop,
Identification of two regulatory elements within the high mobility group box transcription factor XTCF-4.
2001,
Pubmed
,
Xenbase
Ramel,
Repression of the vertebrate organizer by Wnt8 is mediated by Vent and Vox.
2004,
Pubmed
,
Xenbase
Rocheleau,
Wnt signaling and an APC-related gene specify endoderm in early C. elegans embryos.
1997,
Pubmed
Rocheleau,
WRM-1 activates the LIT-1 protein kinase to transduce anterior/posterior polarity signals in C. elegans.
1999,
Pubmed
Roël,
Lef-1 and Tcf-3 transcription factors mediate tissue-specific Wnt signaling during Xenopus development.
2002,
Pubmed
,
Xenbase
Schmidt,
Regulation of dorsal-ventral patterning: the ventralizing effects of the novel Xenopus homeobox gene Vox.
1996,
Pubmed
,
Xenbase
Shin,
MOM-4, a MAP kinase kinase kinase-related protein, activates WRM-1/LIT-1 kinase to transduce anterior/posterior polarity signals in C. elegans.
1999,
Pubmed
Sierra,
The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes.
2006,
Pubmed
Smit,
Wnt activates the Tak1/Nemo-like kinase pathway.
2004,
Pubmed
Sokol,
WNTers in La Jolla.
2007,
Pubmed
Standley,
Maternal XTcf1 and XTcf4 have distinct roles in regulating Wnt target genes.
2006,
Pubmed
,
Xenbase
Thorpe,
nemo-like kinase is an essential co-activator of Wnt signaling during early zebrafish development.
2004,
Pubmed
Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase
Tutter,
Chromatin-specific regulation of LEF-1-beta-catenin transcription activation and inhibition in vitro.
2001,
Pubmed
van de Wetering,
Armadillo coactivates transcription driven by the product of the Drosophila segment polarity gene dTCF.
1997,
Pubmed
van Genderen,
Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice.
1994,
Pubmed
Wei,
HIPK2 represses beta-catenin-mediated transcription, epidermal stem cell expansion, and skin tumorigenesis.
2007,
Pubmed
Zeng,
The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation.
1997,
Pubmed
,
Xenbase
Zeng,
A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.
2005,
Pubmed
,
Xenbase
Zhang,
Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP.
2003,
Pubmed
Zhang,
The beta-catenin/VegT-regulated early zygotic gene Xnr5 is a direct target of SOX3 regulation.
2003,
Pubmed
,
Xenbase
