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Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P.
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Smad family members are newly identified essential intracellular signalling components of the transforming growth factor-beta (TGF-beta) superfamily. Smad2 and Smad3 are structurally highly similar and mediate TGF-beta signals. Smad4 is distantly related to Smads 2 and 3, and forms a heteromeric complex with Smad2 after TGF-beta or activin stimulation. Here we show that Smad2 and Smad3 interacted with the kinase-deficient TGF-beta type I receptor (TbetaR)-I after it was phosphorylated by TbetaR-II kinase. TGF-beta1 induced phosphorylation of Smad2 and Smad3 in Mv1Lu minklung epithelial cells. Smad4 was found to be constitutively phosphorylated in Mv1Lu cells, the phosphorylation level remaining unchanged upon TGF-beta1 stimulation. Similar results were obtained using HSC4 cells, which are also growth-inhibited by TGF-beta. Smads 2 and 3 interacted with Smad4 after TbetaR activation in transfected COS cells. In addition, we observed TbetaR-activation-dependent interaction between Smad2 and Smad3. Smads 2, 3 and 4 accumulated in the nucleus upon TGF-beta1 treatment in Mv1Lu cells, and showed a synergistic effect in a transcriptional reporter assay using the TGF-beta-inducible plasminogen activator inhibitor-1 promoter. Dominant-negative Smad3 inhibited the transcriptional synergistic response by Smad2 and Smad4. These data suggest that TGF-beta induces heteromeric complexes of Smads 2, 3 and 4, and their concomitant translocation to the nucleus, which is required for efficient TGF-beta signal transduction.
Baker,
A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway.
1996, Pubmed,
Xenbase
Baker,
A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway.
1996,
Pubmed
,
Xenbase Chen,
A transcriptional partner for MAD proteins in TGF-beta signalling.
1996,
Pubmed
,
Xenbase Derynck,
Nomenclature: vertebrate mediators of TGFbeta family signals.
1996,
Pubmed
,
Xenbase de Winter,
DPC4 (SMAD4) mediates transforming growth factor-beta1 (TGF-beta1) induced growth inhibition and transcriptional response in breast tumour cells.
1997,
Pubmed Eppert,
MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
1996,
Pubmed
,
Xenbase Franzén,
Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor.
1993,
Pubmed Frolik,
Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts.
1984,
Pubmed Graff,
Xenopus Mad proteins transduce distinct subsets of signals for the TGF beta superfamily.
1996,
Pubmed
,
Xenbase Hahn,
DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1.
1996,
Pubmed Hoodless,
MADR1, a MAD-related protein that functions in BMP2 signaling pathways.
1996,
Pubmed Ichijo,
Biological effects and binding properties of transforming growth factor-beta on human oral squamous cell carcinoma cells.
1990,
Pubmed Jameson,
The antigenic index: a novel algorithm for predicting antigenic determinants.
1988,
Pubmed Lagna,
Partnership between DPC4 and SMAD proteins in TGF-beta signalling pathways.
1996,
Pubmed
,
Xenbase Lechleider,
Serine phosphorylation, chromosomal localization, and transforming growth factor-beta signal transduction by human bsp-1.
1996,
Pubmed Liu,
A human Mad protein acting as a BMP-regulated transcriptional activator.
1996,
Pubmed
,
Xenbase Macías-Silva,
MADR2 is a substrate of the TGFbeta receptor and its phosphorylation is required for nuclear accumulation and signaling.
1996,
Pubmed Massagué,
TGFbeta signaling: receptors, transducers, and Mad proteins.
1996,
Pubmed Massagué,
Serine/threonine kinase receptors: mediators of transforming growth factor beta family signals.
1996,
Pubmed Meersseman,
The C-terminal domain of Mad-like signal transducers is sufficient for biological activity in the Xenopus embryo and transcriptional activation.
1997,
Pubmed
,
Xenbase Nakao,
Identification of Smad2, a human Mad-related protein in the transforming growth factor beta signaling pathway.
1997,
Pubmed
,
Xenbase Riggins,
Mad-related genes in the human.
1996,
Pubmed Savage,
Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components.
1996,
Pubmed Sekelsky,
Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster.
1995,
Pubmed ten Dijke,
Signaling via hetero-oligomeric complexes of type I and type II serine/threonine kinase receptors.
1996,
Pubmed ten Dijke,
Characterization of type I receptors for transforming growth factor-beta and activin.
1994,
Pubmed Thomsen,
Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor.
1996,
Pubmed
,
Xenbase Wrana,
Mechanism of activation of the TGF-beta receptor.
1994,
Pubmed Yamaguchi,
Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction.
1995,
Pubmed Yamashita,
Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.
1995,
Pubmed
,
Xenbase Yingling,
Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth.
1996,
Pubmed Zhang,
Receptor-associated Mad homologues synergize as effectors of the TGF-beta response.
1996,
Pubmed
