| First Author | Nakao A | Year | 1997 |
| Journal | Nature | Volume | 389 |
| Issue | 6651 | Pages | 631-5 |
| PubMed ID | 9335507 | Mgi Jnum | J:43278 |
| Mgi Id | MGI:1097458 | Doi | 10.1038/39369 |
| Citation | Nakao A, et al. (1997) Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling [see comments]. Nature 389(6651):631-5 |
| abstractText | 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. |
