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Published October 16, 1998 | public
Journal Article

Specific Involvement of G Proteins in Regulation of Serum Response Factor-mediated Gene Transcription by Different Receptors


Regulation of serum response factor (SRF)-mediated gene transcription by G protein subunits and G protein-coupled receptors was investigated in transfected NIH3T3 cells and in a cell line that was derived from mice lacking G_(αq) and G_(α11). We found that the constitutively active forms of the α subunits of the G_q and G_(12) class of G proteins, including Gα_q, Gα_(11), Gα_(14), Gα_(16), Gα_(12), and Gα_(13), can activate SRF in NIH3T3 cells. We also found that the type 1 muscarinic receptor (m1R) and α_1-adrenergic receptor (AR)-mediated SRF activation is exclusively dependent on Gα_(q/11), while the receptors for thrombin, lysophosphatidic acid (LPA), thromboxane A2, and endothelin can activate SRF in the absence of Gα_(q/11). Moreover, RGS12 but not RGS2, RGS4, or Axin was able to inhibit Gα_(12) and Gα_(13)-mediated SRF activation. And RGS12, but not other RGS proteins, blocked thrombin- and LPA-mediated SRF activation in the Gα_(q/11)-deficient cells. Therefore, the thrombin, LPA, thromboxane A2, and endothelin receptors may be able to couple to Gα_(12/13). On the contrary, receptors including β_2- and α_2-ARs, m2R, the dopamine receptors type 1 and 2, angiotensin receptors types 1 and 2, and interleukin-8 receptor could not activate SRF in the presence or absence of Gα_(q/11), suggesting that these receptors cannot couple to endogenous G proteins of the G_(12) or G_q classes.

Additional Information

Copyright © 1998 by American Society for Biochemistry and Molecular Biology. (Received for publication, June 17, 1998, and in revised form, July 30, 1998) We thank Huiping Jiang and Mark Betz for reading the manuscript. We also thank Alan Hall, Solvio Gutkind, Sheng-Cai Lin, and F. Costantini for providing cDNAs. This work was supported by National Institutes of Health Grants GM53162 and GM54167 and by the National Heart Association (to D. W.). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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August 19, 2023
October 19, 2023