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 signaling increases beta-catenin abundance and transcription of Wnt-responsive genes. Our previous work suggested that the B56 regulatory subunit of protein phosphatase 2A (PP2A) inhibits Wnt signaling. Okadaic acid (a phosphatase inhibitor) increases, while B56 expression reduces, beta-catenin abundance; B56 also reduces transcription of Wnt-responsive genes. Okadaic acid is a tumor promoter, and the structural A subunit of PP2A is mutated in multiple cancers. Taken together, the evidence suggests that PP2A is a tumor suppressor. However, other studies suggest that PP2A activates Wnt signaling. We now show that the B56, A and catalytic C subunits of PP2A each have ventralizing activity in Xenopus embryos. B56 was epistatically positioned downstream of GSK3beta and axin but upstream of beta-catenin, and axin co-immunoprecipitated B56, A and C subunits, suggesting that PP2A:B56 is in the beta-catenin degradation complex. PP2A appears to be essential for beta-catenin degradation, since beta-catenin degradation was reconstituted in phosphatase-depleted Xenopus egg extracts by PP2A, but not PP1. These results support the hypothesis that PP2A:B56 directly inhibits Wnt signaling and plays a role in development and carcinogenesis.
Baharians,
Autoregulation of protein phosphatase type 2A expression.
1998, Pubmed
Baharians,
Autoregulation of protein phosphatase type 2A expression.
1998,
Pubmed
Barker,
The Yin-Yang of TCF/beta-catenin signaling.
2000,
Pubmed
,
Xenbase
Bosch,
The PR55 and PR65 subunits of protein phosphatase 2A from Xenopus laevis. molecular cloning and developmental regulation of expression.
1995,
Pubmed
,
Xenbase
Brewis,
PPX, a novel protein serine/threonine phosphatase localized to centrosomes.
1993,
Pubmed
Calin,
Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms.
2000,
Pubmed
Campos,
Identification of protein phosphatase-1-binding proteins by microcystin-biotin affinity chromatography.
1996,
Pubmed
Cegielska,
Different oligomeric forms of protein phosphatase 2A activate and inhibit simian virus 40 DNA replication.
1994,
Pubmed
Chen,
A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus.
1994,
Pubmed
Ding,
Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling.
2000,
Pubmed
Fagotto,
Induction of the primary dorsalizing center in Xenopus by the Wnt/GSK/beta-catenin signaling pathway, but not by Vg1, Activin or Noggin.
1997,
Pubmed
,
Xenbase
Götz,
Delayed embryonic lethality in mice lacking protein phosphatase 2A catalytic subunit Calpha.
1998,
Pubmed
Hendrix,
Analysis of subunit isoforms in protein phosphatase 2A holoenzymes from rabbit and Xenopus.
1993,
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
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
Ilyas,
Beta-catenin mutations in cell lines established from human colorectal cancers.
1997,
Pubmed
Janssens,
Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.
2001,
Pubmed
Kao,
The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos.
1988,
Pubmed
,
Xenbase
Kao,
Lithium-induced respecification of pattern in Xenopus laevis embryos.
,
Pubmed
,
Xenbase
Kinzler,
Lessons from hereditary colorectal cancer.
1996,
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
Kishida,
DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.
1999,
Pubmed
Lin,
Protein phosphatase 2A is required for the initiation of chromosomal DNA replication.
1998,
Pubmed
,
Xenbase
McCright,
The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.
1996,
Pubmed
Moon,
From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus.
1998,
Pubmed
,
Xenbase
Murray,
The role of cyclin synthesis and degradation in the control of maturation promoting factor activity.
1989,
Pubmed
,
Xenbase
Paillard,
Identification of a C-rich element as a novel cytoplasmic polyadenylation element in Xenopus embryos.
2000,
Pubmed
,
Xenbase
Pallas,
Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A.
1990,
Pubmed
Peifer,
Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus.
2000,
Pubmed
Price,
Effects of regulatory subunits on the kinetics of protein phosphatase 2A.
2000,
Pubmed
Ratcliffe,
A positive role for the PP2A catalytic subunit in Wnt signal transduction.
2000,
Pubmed
,
Xenbase
Ruediger,
Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the A alpha subunit gene.
2001,
Pubmed
Sakanaka,
Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription.
1998,
Pubmed
Salic,
Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Scharf,
Axis determination in eggs of Xenopus laevis: a critical period before first cleavage, identified by the common effects of cold, pressure and ultraviolet irradiation.
1983,
Pubmed
,
Xenbase
Seeling,
Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A.
1999,
Pubmed
,
Xenbase
Seidensticker,
Biochemical interactions in the wnt pathway.
2000,
Pubmed
Shiomi,
Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system.
1994,
Pubmed
Sparks,
Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer.
1998,
Pubmed
Strovel,
Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription.
2000,
Pubmed
Suganuma,
An alternative theory of tissue specificity by tumor promotion of okadaic acid in glandular stomach of SD rats.
1992,
Pubmed
Sutherland,
Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling.
1993,
Pubmed
Takagi,
Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers.
2000,
Pubmed
Virshup,
Protein phosphatase 2A: a panoply of enzymes.
2000,
Pubmed
Wang,
Alterations of the PPP2R1B gene in human lung and colon cancer.
1998,
Pubmed
Wassarman,
Protein phosphatase 2A positively and negatively regulates Ras1-mediated photoreceptor development in Drosophila.
1996,
Pubmed
Welsh,
Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B.
1993,
Pubmed
Willert,
Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex.
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
Yamamoto,
Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.
1999,
Pubmed
Yang,
Control of protein phosphatase 2A by simian virus 40 small-t antigen.
1991,
Pubmed
