RGS3 and RGS4 are GTPase activating proteins in the heart.
RGS family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha subtypes when tested in vitro and in vivo. Although the function of RGS proteins in cardiac physiology is unknown, their ability to deactivate Galpha subunits suggests that they may inhibit the action of muscarinic, alpha-adrenergic, endothelin, and other agonists. To evaluate the role of RGS family members in the regulation of cardiac physiology, we investigated the expression pattern of two RGS genes in normal and diseased rat heart tissue. RGS3 and RGS4 mRNAs and proteins were detected in adult myocardium. RGS3 and RGS4 gene expression was markedly enhanced in two model systems of cardiac hypertrophy: growth factor-stimulated cultured neonatal rat cardiomyocytes and pulmonary artery-banded (PAB) mice. RGS3 and RGS4 mRNA levels were reduced in failing myocardium obtained from SHHF/Mcc-fa(cp) (SHHF) rats. These findings support the hypothesis that RGS gene expression is highly regulated in myocardium and imply that RGS family members play an important role in the regulation of cardiac function.
Zhang
S
S
Center for Cardiovascular Research, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Watson
N
N
Zahner
J
J
Rottman
J N
JN
Blumer
K J
KJ
Muslin
A J
AJ
D000595:Amino Acid Sequence; D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020710:RGS Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D012097:Repressor Proteins
D020690:GTPase-Activating Proteins; D011506:Proteins; D020710:RGS Proteins; C485898:RGS3 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; C415085:Rgs3 protein, mouse; C437714:Rgs3 protein, rat; C098799:RGS4 protein; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins