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

@article{citeulike:3768133, 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.}, author = {Nakao, A. and Afrakhte, M. and Mor\'{e}n, A. and Nakayama, T. and Christian, J. L. and Heuchel, R. and Itoh, S. and Kawabata, M. and Heldin, N. E. and Heldin, C. H. and ten Dijke, P.}, citeulike-article-id = {3768133}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/39369}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/9335507}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=9335507}, day = {9}, doi = {10.1038/39369}, issn = {0028-0836}, journal = {Nature}, keywords = {smad7, tgfb}, month = {October}, number = {6651}, pages = {631--635}, posted-at = {2008-12-31 04:10:08}, priority = {2}, title = {Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling.}, url = {http://dx.doi.org/10.1038/39369}, volume = {389}, year = {1997} }

TY - JOUR ID - citeulike:3768133 L3 - citeulike-article-id:3768133 N2 - 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. IS - 6651 JF - Nature SN - 0028-0836 EP - 635 TI - Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. VL - 389 SP - 631 KW - smad7 KW - tgfb AU - Nakao, A AU - Afrakhte, M AU - Morén, A AU - Nakayama, T AU - Christian, JL AU - Heuchel, R AU - Itoh, S AU - Kawabata, M AU - Heldin, NE AU - Heldin, CH AU - ten Dijke, P PY - 1997/10/09/ UR - http://dx.doi.org/10.1038/39369 ER -