Specific involvement of G proteins in regulation of serum response factor-mediated gene transcription by different receptors

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 a subunits of the G(q) and 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 Gaα(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(q) classes.