Background - RGS family members are GTPase-activating proteins for heterotrimeric G(q) and G(i) proteins. RGS genes are expressed in heart tissue and in cultured cardiomyocytes. There is evidence that altered RGS gene expression may contribute to the pathogenesis of cardiac hypertrophy and failure. Methods and Results - We investigated the ability of RGS proteins to block G-protein signaling in vivo by using a cultured cardiomyocyte transfection system. Endothelin-1, angiotensin II, and phenylephrine signal through G(q) or G(i) family members and promote the hypertrophy of cardiomyocytes. We found that phenylephrine-mediated and endothelin-1- mediated induction of the atrial natriuretic factor and myosin light chain-2 genes was inhibited in cells that were transfected with RGS4. Phenylephrine- mediated gene induction was not inhibited in cells that were transfected with N128A-RGS4, a point mutant form that lacks GTPase-activating protein activity. Phenylephrine-mediated myofilament organization and cell growth were also blocked in cells by RGS4. Conclusions - These results demonstrate that RGS protein can inhibit G-protein-mediated signaling in vivo and suggest that increased expression of RGS protein may be a counterregulatory mechanism to inhibit G protein signaling.
- Atrial natriuretic factor
- Growth substances