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PMID:9288972
| Citation |
Chen, X, Weisberg, E, Fridmacher, V, Watanabe, M, Naco, G and Whitman, M (1997) Smad4 and FAST-1 in the assembly of activin-responsive factor. Nature 389:85-9 |
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| Abstract |
Members of the TGF-beta superfamily of signalling molecules work by activating transmembrane receptors with phosphorylating activity (serine-threonine kinase receptors); these in turn phosphorylate and activate SMADs, a class of signal transducers. Activins are growth factors that act primarily through Smad2, possibly in partnership with Smad4, which forms heteromeric complexes with different ligand-specific SMADs after activation. In frog embryos, Smad2 participates in an activin-responsive factor (ARF), which then binds to a promoter element of the Mix.2 gene. The principal DNA-binding component of ARF is FAST-1, a transcription factor with a novel winged-helix structure. We now report that Smad4 is present in ARF, and that FAST-1, Smad4 and Smad2 co-immunoprecipitate in a ligand-regulated fashion. We have mapped the site of interaction between FAST-1 and Smad2/Smad4 to a novel carboxy-terminal domain of FAST-1, and find that overexpression of this domain specifically inhibits activin signalling. In a yeast two-hybrid assay, the FAST-1 carboxy terminus interacts with Smad2 but not Smad4. Deletion mutants of the FAST-1 carboxy terminus that still participate in ligand-regulated Smad2 binding no longer associated with Smad4 or ARF. These results indicate that Smad4 stabilizes a ligand-stimulated Smad2-FAST-1 complex as an active DNA-binding factor. |
| Links |
PubMed Online version:10.1038/38008 |
| Keywords |
Activins; Animals; Binding Sites; DNA/metabolism; DNA-Binding Proteins/metabolism; Electrophoresis; Embryo, Nonmammalian/metabolism; Epitopes; Forkhead Transcription Factors; Humans; Inhibins/antagonists & inhibitors; Inhibins/metabolism; Macromolecular Substances; Mice; Molecular Sequence Data; Precipitin Tests; Signal Transduction; Smad2 Protein; Smad4 Protein; Trans-Activators/metabolism; Transcription Factors/metabolism; Xenopus; Xenopus Proteins |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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