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 Galphaq and Galpha11. We found that the constitutively active forms of the alpha subunits of the Gq and G12 class of G proteins, including Galphaq, Galpha11, Galpha14, Galpha16, Galpha12, and Galpha13, can activate SRF in NIH3T3 cells. We also found that the type 1 muscarinic receptor (m1R) and alpha1-adrenergic receptor (AR)-mediated SRF activation is exclusively dependent on Galphaq/11, while the receptors for thrombin, lysophosphatidic acid (LPA), thromboxane A2, and endothelin can activate SRF in the absence of Galphaq/11. Moreover, RGS12 but not RGS2, RGS4, or Axin was able to inhibit Galpha12 and Galpha13-mediated SRF activation. And RGS12, but not other RGS proteins, blocked thrombin- and LPA-mediated SRF activation in the Galphaq/11-deficient cells. Therefore, the thrombin, LPA, thromboxane A2, and endothelin receptors may be able to couple to Galpha12/13. On the contrary, receptors including beta2- and alpha2-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 Galphaq/11, suggesting that these receptors cannot couple to endogenous G proteins of the G12 or Gq classes.
Mao
J
J
Department of Pharmacology and Physiology, University of Rochester, New York 14642, USA.
Yuan
H
H
Xie
W
W
Simon
M I
MI
Wu
D
D
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004357:Drug Synergism; D016232:Endothelins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D005786:Gene Expression Regulation; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D026362:Serum Response Factor; D013917:Thrombin / Q000494:pharmacology; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D016232:Endothelins; D020690:GTPase-Activating Proteins; D008246:Lysophospholipids; D009687:Nuclear Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D026362:Serum Response Factor; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D013917:Thrombin; D019204:GTP-Binding Proteins