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Molecular Pharmacology Fast Forward
First published on February 20, 2008; DOI: 10.1124/mol.108.044990

0026-895X/08/7305-1356-1361$20.00
Mol Pharmacol 73:1356-1361, 2008

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Accelerated Communication

Regulation of Smad-Mediated Gene Transcription by RGS3

Douglas M. Yau, Nan Sethakorn, Sebastien Taurin, Steven Kregel, Nathan Sandbo, Blanca Camoretti-Mercado, Anne I. Sperling, and Nickolai O. Dulin

Department of Medicine, the University of Chicago, Chicago, Illinois

Regulator of G protein signaling (RGS) proteins are united into a family by the presence of the homologous RGS domain that binds the {alpha} subunits of heterotrimeric G proteins and accelerates their GTPase activity. A member of this family, RGS3 regulates the signaling mediated by Gq and Gi proteins by binding the corresponding G{alpha} subunits. Here we show that RGS3 interacts with the novel partners Smad2, Smad3, and Smad4—the transcription factors that are activated through a transforming growth factor-β (TGF-β) receptor signaling. This interaction is mediated by the region of RGS3 outside of the RGS domain and by Smad's Mad homology 2 domain. Overexpression of RGS3 results in inhibition of Smad-mediated gene transcription. RGS3 does not affect TGF-β-induced Smad phosphorylation, but it prevents heteromerization of Smad3 with Smad4, which is required for transcriptional activity of Smads. This translates to functional inhibition of TGF-β-induced myofibroblast differentiation by RGS3. In conclusion, this study identifies a novel, noncanonical role of RGS3 in regulation of TGF-β signaling through its interaction with Smads and interfering with Smad heteromerization.

Received for publication January 4, 2008.

Accepted for publication February 19, 2008.

Address correspondence to: Dr. Nickolai Dulin, Section of Pulmonary and Critical Care Medicine, the University of Chicago Department of Medicine, 5841 S. Maryland Ave, MC 6076, Chicago, IL 60637. E-mail: ndulin{at}medicine.bsd.uchicago.edu




This article has been cited by other articles:


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N. Sandbo, S. Kregel, S. Taurin, S. Bhorade, and N. O. Dulin
Critical Role of Serum Response Factor in Pulmonary Myofibroblast Differentiation Induced by TGF-{beta}
Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 332 - 338.
[Abstract] [Full Text] [PDF]


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