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(Circulation. 1999;99:441-447.)
© 1999 American Heart Association, Inc.

Basic Science Reports

RGS4 Inhibits G-Protein Signaling in Cardiomyocytes

Praveen Tamirisa, MD; Kendall J. Blumer, PhD; Anthony J. Muslin, MD

From the Center for Cardiovascular Research, Department of Medicine, and the Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Mo.

Correspondence to Anthony J. Muslin, Center for Cardiovascular Research, Box 8086, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110. E-mail amuslin{at}im.wustl.edu

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.

Key Words: hypertrophy • genes • growth substances • atrial natriuretic factor • proteins

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