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.
EMBO J
2007 Mar 21;266:1511-21. doi: 10.1038/sj.emboj.7601607.
Show Gene links
Show Anatomy links
Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex.
Luo W
,
Peterson A
,
Garcia BA
,
Coombs G
,
Kofahl B
,
Heinrich R
,
Shabanowitz J
,
Hunt DF
,
Yost HJ
,
Virshup DM
.
???displayArticle.abstract???
The Wnt/beta-catenin signaling pathway is critical in both cellular proliferation and organismal development. However, how the beta-catenin degradation complex is inhibited upon Wnt activation remains unclear. Using a directed RNAi screen we find that protein phosphatase 1 (PP1), a ubiquitous serine/threonine phosphatase, is a novel potent positive physiologic regulator of the Wnt/beta-catenin signaling pathway. PP1 expression synergistically activates, and inhibition of PP1 inhibits, Wnt/beta-catenin signaling in Drosophila and mammalian cells as well as in Xenopus embryos. The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin. Inhibition of PP1 leads to enhanced phosphorylation of specific sites on axin by casein kinase I. Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity. Specific inhibition of PP1 in this pathway may offer therapeutic approaches to disorders with increased beta-catenin signaling.
Alam,
Reporter genes: application to the study of mammalian gene transcription.
1990, Pubmed
Alam,
Reporter genes: application to the study of mammalian gene transcription.
1990,
Pubmed
Amit,
Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway.
2002,
Pubmed
Castellone,
Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis.
2005,
Pubmed
Ceulemans,
Functional diversity of protein phosphatase-1, a cellular economizer and reset button.
2004,
Pubmed
Chen,
Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C.
2000,
Pubmed
,
Xenbase
Dajani,
Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex.
2003,
Pubmed
DasGupta,
Functional genomic analysis of the Wnt-wingless signaling pathway.
2005,
Pubmed
Davidson,
Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction.
2005,
Pubmed
,
Xenbase
Deng,
Phosphorylation of the myosin phosphatase inhibitors, CPI-17 and PHI-1, by integrin-linked kinase.
2002,
Pubmed
Ding,
Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling.
2000,
Pubmed
Dombrádi,
Cloning of the fourth functional gene for protein phosphatase 1 in Drosophila melanogaster from its chromosomal location.
1993,
Pubmed
Dombrádi,
Drosophila contains three genes that encode distinct isoforms of protein phosphatase 1.
1990,
Pubmed
Doonan,
A cDNA encoding rabbit muscle protein phosphatase 1 alpha complements the Aspergillus cell cycle mutation, bimG11.
1991,
Pubmed
Eto,
A novel phosphoprotein inhibitor of protein type-1 phosphatase holoenzymes.
1999,
Pubmed
Favre,
Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin.
1997,
Pubmed
Furnari,
Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain.
1997,
Pubmed
Gao,
Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex.
2002,
Pubmed
,
Xenbase
Hsu,
Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain.
1999,
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
Jho,
A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression.
1999,
Pubmed
Komeili,
Roles of phosphorylation sites in regulating activity of the transcription factor Pho4.
1999,
Pubmed
Korinek,
Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma.
1997,
Pubmed
Lee,
The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway.
2003,
Pubmed
,
Xenbase
Lee,
Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.
2001,
Pubmed
,
Xenbase
Li,
Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus.
2001,
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,
B56-associated protein phosphatase 2A is required for survival and protects from apoptosis in Drosophila melanogaster.
2002,
Pubmed
Liu,
Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism.
2002,
Pubmed
,
Xenbase
Liu,
Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins.
2005,
Pubmed
Logan,
The Wnt signaling pathway in development and disease.
2004,
Pubmed
Luo,
Axin: a master scaffold for multiple signaling pathways.
2004,
Pubmed
Mao,
Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway.
2001,
Pubmed
Martin,
Subfemtomole MS and MS/MS peptide sequence analysis using nano-HPLC micro-ESI fourier transform ion cyclotron resonance mass spectrometry.
2000,
Pubmed
Naerum,
Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors.
2002,
Pubmed
Okano,
Genomic organization and functional analysis of the murine protein phosphatase 1c gamma (Ppp1cc) gene.
1997,
Pubmed
Pai,
Negative regulation of Armadillo, a Wingless effector in Drosophila.
1997,
Pubmed
Polakis,
Wnt signaling and cancer.
2000,
Pubmed
Rena,
D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a.
2004,
Pubmed
Resink,
Characterisation of a reconstituted Mg-ATP-dependent protein phosphatase.
1983,
Pubmed
Reya,
Wnt signalling in stem cells and cancer.
2005,
Pubmed
Salic,
Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Seeling,
Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A.
1999,
Pubmed
,
Xenbase
Shevchenko,
Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels.
1996,
Pubmed
Strovel,
Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription.
2000,
Pubmed
Swiatek,
Regulation of casein kinase I epsilon activity by Wnt signaling.
2004,
Pubmed
,
Xenbase
Tamai,
A mechanism for Wnt coreceptor activation.
2004,
Pubmed
,
Xenbase
Tolwinski,
Wg/Wnt signal can be transmitted through arrow/LRP5,6 and Axin independently of Zw3/Gsk3beta activity.
2003,
Pubmed
Tountas,
Migration and retraction of endothelial and epithelial cells require PHI-1, a specific protein-phosphatase-1 inhibitor protein.
2004,
Pubmed
van Amerongen,
Re-evaluating the role of Frat in Wnt-signal transduction.
2005,
Pubmed
,
Xenbase
Willert,
Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.
1999,
Pubmed
Xu,
Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair.
2004,
Pubmed
Yamamoto,
Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.
1999,
Pubmed
Yanagawa,
Identification and characterization of a novel line of Drosophila Schneider S2 cells that respond to wingless signaling.
1998,
Pubmed
Yost,
GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis.
1998,
Pubmed
,
Xenbase
Zeng,
A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.
2005,
Pubmed
,
Xenbase
