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Nature October 9, 1997; 389 (6651): 631-5.

Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling.

Nakao A , Afrakhte M , Morén A , Nakayama T , Christian JL , Heuchel R , Itoh S , Kawabata M , Heldin NE , Heldin CH , ten Dijke P .

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.

PubMed ID: 9335507
Article link: Nature

Species referenced: Xenopus laevis
Genes referenced: smad2 smad3 smad4 smad4.2 smad6 smad6.2 smad7 tgfb1

References :
Whitman, Signal transduction. Feedback from inhibitory SMADs. 1997, Pubmed