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PMID:9436979

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Citation

Hata, A, Lagna, G, Massagué, J and Hemmati-Brivanlou, A (1998) Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 12:186-97

Abstract

Bone morphogenetic protein (BMP) receptors signal by phosphorylating Smad1, which then associates with Smad4; this complex moves into the nucleus and activates transcription. Here we report the existence of a natural inhibitor of this process, Smad6, a longer version of the previously reported JV15-1. In Xenopus embryos and in mammalian cells, Smad6 specifically blocks signaling by the BMP/Smad1 pathway. Smad6 inhibits BMP/Smad1 signaling without interfering with receptor-mediated phosphorylation of Smad1. Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy.

Links

PubMed PMC316444

Keywords

Amino Acid Sequence; Animals; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Proteins/antagonists & inhibitors; COS Cells; Cells, Cultured; DNA-Binding Proteins/antagonists & inhibitors; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Ectoderm/physiology; Genes, Tumor Suppressor/physiology; Humans; Immunoblotting; Molecular Sequence Data; Receptors, Cell Surface/physiology; Receptors, Growth Factor; Signal Transduction/genetics; Smad Proteins; Smad1 Protein; Smad4 Protein; Smad6 Protein; Trans-Activators/physiology; Transfection; Xenopus; Xenopus Proteins

Significance

Annotations

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

HUMAN:SMAD6

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15797

F

Seeded From UniProt

complete

HUMAN:SMAD4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15797

F

Seeded From UniProt

complete

HUMAN:SMAD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43541

F

Seeded From UniProt

complete

HUMAN:SMAD1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13485

F

Seeded From UniProt

complete

HUMAN:SMAD1

enables

GO:0070411: I-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43541

F

Seeded From UniProt

complete

HUMAN:SMAD2

involved_in

GO:0007352: zygotic specification of dorsal/ventral axis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD6

enables

GO:0070698: type I activin receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SMAD6

enables

GO:0070412: R-SMAD binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15797

F

Seeded From UniProt

complete

HUMAN:SMAD6

involved_in

GO:0060394: negative regulation of pathway-restricted SMAD protein phosphorylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD6

enables

GO:0034713: type I transforming growth factor beta receptor binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:SMAD6

involved_in

GO:0030514: negative regulation of BMP signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD6

involved_in

GO:0010991: negative regulation of SMAD protein complex assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD6

involved_in

GO:0007352: zygotic specification of dorsal/ventral axis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD6

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O43541

F

Seeded From UniProt

complete


See also

References

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