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 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.