RGS4 inhibits G-protein signaling in cardiomyocytes
RGS4 inhibits G-protein signaling in cardiomyocytes
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DOI：
10.1161/01.cir.99.3.441
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发表时间：
1999-01-26
期刊：
影响因子：
37.8
通讯作者：
Muslin, AJ
中科院分区：
文献类型：
--
作者：
Tamirisa, P;Blumer, KJ;Muslin, AJ
背景-RGS 家族成员是异三聚体 G(q) 和 G(i) 蛋白的 GTP 酶激活蛋白。 RGS 基因在心脏组织和培养的心肌细胞中表达。有证据表明，RGS 基因表达的改变可能导致心脏肥大和衰竭的发病机制。方法和结果-我们通过使用培养的心肌细胞转染系统研究了 RGS 蛋白在体内阻断 G 蛋白信号传导的能力。内皮素-1、血管紧张素 II 和去氧肾上腺素通过 G(q) 或 G(i) 家族成员发出信号并促进心肌细胞肥大。我们发现，在用 RGS4 转染的细胞中，去氧肾上腺素介导和内皮素 1 介导的心房钠尿因子和肌球蛋白轻链 2 基因的诱导受到抑制。在用 N128A-RGS4（一种缺乏 GTP 酶激活蛋白活性的点突变形式）转染的细胞中，去氧肾上腺素介导的基因诱导并未受到抑制。细胞中去氧肾上腺素介导的肌丝组织和细胞生长也被RGS4阻断。结论-这些结果证明RGS蛋白可以抑制体内G蛋白介导的信号传导，并表明RGS蛋白表达的增加可能是抑制G蛋白信号传导的反调节机制。
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.