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

doi:10.1074/jbc.273.42.27118

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

From the Department of Pharmacology and Physiology, University of Rochester, New York 14642 and the ^‡Division of Biology, California Institute of Technology, Pasadena, California 91125

Abstract

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 Gα_q and Gα₁₁. We found that the constitutively active forms of the α subunits of the G_qand G₁₂ class of G proteins, including Gα_q, Gα₁₁, Gα₁₄, Gα₁₆, Gα₁₂, and Gα₁₃, can activate SRF in NIH3T3 cells. We also found that the type 1 muscarinic receptor (m1R) and α₁-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 Gα₁₂ and Gα₁₃-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 β₂- and α₂-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 G₁₂ or G_qclasses.

Footnotes

↵* 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.
↵§ To whom correspondence should be addressed. E-mail:wud{at}pharmacol.rochester.edu.
↵2 D. Wu, unpublished data.
↵3 J. Mao and D. Wu, unpublished data.
Abbreviations:

LPA

lysophosphatidic acid

AR

adrenergic receptor

AT

angiotensin

C3

C. butulinum C3 transferase

CRE

cAMP response element

LacZ

β-galactosidase

GPCR

G protein-coupled receptors

IL-8

interleukin-8

m1R and m2R

muscarinic cholinergic receptor type 1 and type 2, respectively

Ptx

pertussis toxin

RGS

regulator of G protein signaling

SRE

serum response element

SRF

serum response factor

GFP

green fluorescence protein.
- Received June 17, 1998.
- Revision received July 30, 1998.