RGS4 inhibits G-protein signaling in cardiomyocytes

Background-RGS family members are GTPase-activating proteins for heterotrim eric G(q) and G(i) proteins. RGS genes are expressed in heart tissue and in cultured cardiomyocytes. There is evidence that altered RGS gene expressio n 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 sy stem. Endothelin-1, angiotensin II, and phenylephrine signal through G(q) o r G(i) family members and promote the hypertrophy of cardiomyocytes. We fou nd that phenylephrine-mediated and endothelin-1-mediated induction of the a trial natriuretic factor and myosin light chain-2 genes was inhibited in ce lls that were transfected with RGS4. Phenylephrine-mediated gene induction was not inhibited in cells that were transfected with N128A-RGS4, a point m utant form that lacks GTPase-activating protein activity. Phenylephrine-med iated myofilament organization and cell growth were also blocked in cells b y RGS4. Conclusions-These results demonstrate that RGS protein can inhibit G-protei n-mediated signaling in vivo and suggest that increased expression of RGS p rotein may be a counterregulatory mechanism to inhibit G protein signaling.