Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling - PubMed (original) (raw)
. 1997 Oct 9;389(6651):631-5.
doi: 10.1038/39369.
Affiliations
- PMID: 9335507
- DOI: 10.1038/39369
Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling
A Nakao et al. Nature. 1997.
Abstract
TGF-beta signals from the membrane to the nucleus through serine/threonine kinase receptors and their downstream effectors, termed SMAD proteins. The activated TGF-beta receptor induces phosphorylation of two such proteins, Smad2 and Smad3, which form hetero-oligomeric complex(es) with Smad4/DPC4 that translocate to the nucleus, where they then regulate transcriptional responses. However, the mechanisms by which the intracellular signals of TGF-beta are switched off are unclear. Here we report the identification of Smad7, which is related to Smad6. Transfection of Smad7 blocks responses mediated by TGF-beta in mammalian cells, and injection of Smad7 RNA into Xenopus embryos blocks activin/TGF-beta signalling. Smad7 associates stably with the TGF-beta receptor complex, but is not phosphorylated upon TGF-beta stimulation. TGFbeta-mediated phosphorylation of Smad2 and Smad3 is inhibited by Smad7, indicating that the antagonistic effect of Smad7 is exerted at this important regulatory step. TGF-beta rapidly induces expression of Smad7 mRNA, suggesting that Smad7 may participate in a negative feedback loop to control TGF-beta responses.
Comment in
- Signal transduction. Feedback from inhibitory SMADs.
Whitman M. Whitman M. Nature. 1997 Oct 9;389(6651):549-51. doi: 10.1038/39202. Nature. 1997. PMID: 9335489 No abstract available.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous