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 alpha(q) and G alpha(11). We found that the constitutively active forms of the alpha subunits of the G(q) and G(12) class of G proteins, including G alpha(q), G alpha(11), G alpha(14), G alpha(16), G alpha(12), and G alpha(13), can activate SRF in NIH3T3 cells. me also found that the type 1 muscarinic receptor (m1R) and alpha(1)-adrenergic receptor (AR)-mediated SRF activation is exclusively dependent on G alpha(q/11), while the receptors for thrombin, lysophosphatidic acid (LPA), thromboxane A2, and endothelin can activate SRF in the absence of G alpha(q/11). Moreover, RGS12 but not RGS2, RGS4, or Axin was able to inhibit G alpha(12) and G alpha(13)-mediated SRF activation. And RGS12, but not other RGS proteins, blocked thrombin- and LPA-mediated SRF activation in the G alpha(q/11)-deficient cells. Therefore, the thrombin, LPA, thromboxane A2, and endothelin receptors may be able to couple to G alpha(12/13). On the contrary, receptors including beta(2)- and alpha(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 G alpha(q/11), suggesting that these receptors cannot couple to endogenous G proteins of the G(12) or G(q) classes.