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.
Development
2008 Sep 01;13517:2927-37. doi: 10.1242/dev.020842.
Show Gene links
Show Anatomy links
Two highly related regulatory subunits of PP2A exert opposite effects on TGF-beta/Activin/Nodal signalling.
Batut J
,
Schmierer B
,
Cao J
,
Raftery LA
,
Hill CS
,
Howell M
.
???displayArticle.abstract???
We identify Balpha (PPP2R2A) and Bdelta (PPP2R2D), two highly related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-beta/Activin/Nodal signalling that affect the pathway in opposite ways. Knockdown of Balpha in Xenopus embryos or mammalian tissue culture cells suppresses TGF-beta/Activin/Nodal-dependent responses, whereas knockdown of Bdelta enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit Twins. We show that, in vertebrates, Balpha enhances TGF-beta/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bdelta negatively modulates these pathways by restricting receptor activity. Thus, these highly related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-beta/Activin/Nodal signalling to elicit opposing biological outcomes.
Fig. 2. Manipulating the expression of Bα and Bδ in Xenopus embryos has opposing effects on Activin/Nodal target gene expression. (A) In situ hybridisation of gastrula-stage embryos injected with either a morpholino control (MoC) or a specific morpholino against Xenopus Bα (MoBα) or Bδ (MoBδ), or with Flag-tagged mouse Bδ mRNA (Bδ) at the one-cell stage. The probes used were against gsc or Xbra. Staining was visualised with BM purple. There is increased staining for both Xbra and Gsc in Bδ morphants, and decreased staining in Bα morphants and embryos overexpressing Bδ. (B) Analysis of gene expression by q-PCR. Total RNA was isolated from stage 10.5 embryos that had been injected at the one-cell stage with either morpholino control, or morpholinos against Bα or Bδ. Expression levels are normalised to ornithine decarboxylase (ODC).
Adams,
Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes.
2005, Pubmed
Adams,
Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes.
2005,
Pubmed
Bajpai,
Drosophila Twins regulates Armadillo levels in response to Wg/Wnt signal.
2004,
Pubmed
Bardwell,
The POZ domain: a conserved protein-protein interaction motif.
1994,
Pubmed
Batut,
Kinesin-mediated transport of Smad2 is required for signaling in response to TGF-beta ligands.
2007,
Pubmed
,
Xenbase
Bennett,
PP1 binds Sara and negatively regulates Dpp signaling in Drosophila melanogaster.
2002,
Pubmed
Brand,
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
1993,
Pubmed
Brummel,
The Drosophila activin receptor baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development.
1999,
Pubmed
Chen,
Identification of phosphatases for Smad in the BMP/DPP pathway.
2006,
Pubmed
Di Guglielmo,
Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover.
2003,
Pubmed
Dorey,
A novel Cripto-related protein reveals an essential role for EGF-CFCs in Nodal signalling in Xenopus embryos.
2006,
Pubmed
,
Xenbase
Feng,
Specificity and versatility in tgf-beta signaling through Smads.
2005,
Pubmed
Griswold-Prenner,
Physical and functional interactions between type I transforming growth factor beta receptors and Balpha, a WD-40 repeat subunit of phosphatase 2A.
1998,
Pubmed
Henderson,
Identification of a novel Drosophila SMAD on the X chromosome.
1998,
Pubmed
Ho,
Inhibitor-resistant type I receptors reveal specific requirements for TGF-beta signaling in vivo.
2006,
Pubmed
,
Xenbase
Howell,
Xenopus Smad4beta is the co-Smad component of developmentally regulated transcription factor complexes responsible for induction of early mesodermal genes.
1999,
Pubmed
,
Xenbase
Howell,
A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3) cooperates with XFast-1 in regulating gastrulation movements.
2002,
Pubmed
,
Xenbase
Janssens,
PP2A: the expected tumor suppressor.
2005,
Pubmed
Janssens,
Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling.
2001,
Pubmed
Jullien,
Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction.
2005,
Pubmed
,
Xenbase
Knockaert,
Unique players in the BMP pathway: small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling.
2006,
Pubmed
,
Xenbase
Kretzschmar,
A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras.
1999,
Pubmed
Lee,
Timing of endogenous activin-like signals and regional specification of the Xenopus embryo.
2001,
Pubmed
,
Xenbase
Levy,
Smad4 dependency defines two classes of transforming growth factor {beta} (TGF-{beta}) target genes and distinguishes TGF-{beta}-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses.
2005,
Pubmed
Lin,
PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling.
2006,
Pubmed
Marquez,
Transgenic analysis of the Smad family of TGF-beta signal transducers in Drosophila melanogaster suggests new roles and new interactions between family members.
2001,
Pubmed
Massagué,
Smad transcription factors.
2005,
Pubmed
Mayer-Jaekel,
The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase.
1993,
Pubmed
Nicolás,
Attenuation of the TGF-beta-Smad signaling pathway in pancreatic tumor cells confers resistance to TGF-beta-induced growth arrest.
2003,
Pubmed
Nicolás,
Analysis of Smad nucleocytoplasmic shuttling in living cells.
2004,
Pubmed
Parker,
The divergent TGF-beta ligand Dawdle utilizes an activin pathway to influence axon guidance in Drosophila.
2006,
Pubmed
Peter,
Mapping and identification of essential gene functions on the X chromosome of Drosophila.
2002,
Pubmed
Petritsch,
TGF-beta inhibits p70 S6 kinase via protein phosphatase 2A to induce G(1) arrest.
2000,
Pubmed
Sathyanarayanan,
Posttranslational regulation of Drosophila PERIOD protein by protein phosphatase 2A.
2004,
Pubmed
Satow,
Dullard promotes degradation and dephosphorylation of BMP receptors and is required for neural induction.
2006,
Pubmed
,
Xenbase
Schier,
Axis formation and patterning in zebrafish.
2001,
Pubmed
Schmierer,
Kinetic analysis of Smad nucleocytoplasmic shuttling reveals a mechanism for transforming growth factor beta-dependent nuclear accumulation of Smads.
2005,
Pubmed
,
Xenbase
Schmierer,
TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.
2007,
Pubmed
Serpe,
The metalloprotease tolloid-related and its TGF-beta-like substrate Dawdle regulate Drosophila motoneuron axon guidance.
2006,
Pubmed
Shi,
GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor.
2004,
Pubmed
Smith,
Mesoderm-inducing factors in early vertebrate development.
1993,
Pubmed
Strack,
Overexpression of the protein phosphatase 2A regulatory subunit Bgamma promotes neuronal differentiation by activating the MAP kinase (MAPK) cascade.
2002,
Pubmed
Strack,
Cloning and characterization of B delta, a novel regulatory subunit of protein phosphatase 2A.
1999,
Pubmed
Strack,
Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits.
2002,
Pubmed
Sun,
Activation and roles of ALK4/ALK7-mediated maternal TGFbeta signals in zebrafish embryo.
2006,
Pubmed
Tada,
Non-canonical Wnt signalling and regulation of gastrulation movements.
2002,
Pubmed
,
Xenbase
ten Dijke,
New insights into TGF-beta-Smad signalling.
2004,
Pubmed
Uemura,
Mutation of twins encoding a regulator of protein phosphatase 2A leads to pattern duplication in Drosophila imaginal discs.
1993,
Pubmed
Van Kanegan,
Distinct protein phosphatase 2A heterotrimers modulate growth factor signaling to extracellular signal-regulated kinases and Akt.
2005,
Pubmed
Whitman,
Nodal signaling in early vertebrate embryos: themes and variations.
2001,
Pubmed
,
Xenbase
Wieser,
GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex.
1995,
Pubmed
Zhang,
Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors.
2004,
Pubmed
Zheng,
TGF-beta signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain.
2003,
Pubmed
