GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:9311995

From GONUTS
Jump to: navigation, search
Citation

Nakao, A, Imamura, T, Souchelnytskyi, S, Kawabata, M, Ishisaki, A, Oeda, E, Tamaki, K, Hanai, J, Heldin, CH, Miyazono, K and ten Dijke, P (1997) TGF-beta receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J. 16:5353-62

Abstract

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 mink lung 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.

Links

PubMed PMC1170167 Online version:10.1093/emboj/16.17.5353

Keywords

Activin Receptors, Type I; Amino Acid Sequence; Animals; Antibody Specificity; Biological Transport; COS Cells; Cell Nucleus/metabolism; DNA-Binding Proteins/immunology; DNA-Binding Proteins/metabolism; Epithelial Cells; Genes, Reporter; Humans; Lung/cytology; Mink; Models, Biological; Molecular Sequence Data; Phosphorylation; Protein Binding; Protein-Serine-Threonine Kinases/metabolism; Receptors, Transforming Growth Factor beta/metabolism; Signal Transduction; Smad2 Protein; Smad3 Protein; Smad4 Protein; Trans-Activators/immunology; Trans-Activators/metabolism; Transcription, Genetic; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TGFR1

involved_in

GO:0010862: positive regulation of pathway-restricted SMAD protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFR1

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15796

F

Seeded From UniProt

complete

HUMAN:TGFR1

enables

GO:0046332: SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84022

F

Seeded From UniProt

complete

HUMAN:TGFR1

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD3

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD3

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD4

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD4

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0070410: co-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13485

F

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0005160: transforming growth factor beta receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P36897

F

Seeded From UniProt

complete

HUMAN:SMAD2

enables

GO:0070412: R-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84022

F

Seeded From UniProt

complete

HUMAN:SMAD2

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD2

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD3

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD3

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD3

enables

GO:0005160: transforming growth factor beta receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P36897

F

Seeded From UniProt

complete

HUMAN:SMAD3

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD3

enables

GO:0070410: co-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13485

F

Seeded From UniProt

complete

HUMAN:SMAD3

enables

GO:0070412: R-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15796

F

Seeded From UniProt

complete

HUMAN:SMAD4

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD4

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SMAD4

involved_in

GO:0045893: positive regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD4

enables

GO:0070412: R-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P84022

F

Seeded From UniProt

complete

HUMAN:SMAD4

enables

GO:0070412: R-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15796

F

Seeded From UniProt

complete

HUMAN:BMP7

involved_in

GO:0010862: positive regulation of pathway-restricted SMAD protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.