Regulation of G Protein–Coupled Receptor Signaling By Scaffold Proteins G Protein–Coupled Receptor Oligomerization: Implications for G Protein Activation and Cell Signaling Multi-Tasking RGS Proteins in the Heart: The Next Therapeutic Target?
Regulation of G Protein–Coupled Receptor Signaling By Scaffold Proteins G Protein–Coupled Receptor Oligomerization: Implications for G Protein Activation and Cell Signaling Multi-Tasking RGS Proteins in the Heart: The Next Therapeutic Target?
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发表时间：
2005
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通讯作者：
Evan L. Riddle;R. Schwartzman;M. Bond;P. Insel
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作者：
Evan L. Riddle;R. Schwartzman;M. Bond;P. Insel
G蛋白信号调节蛋白（Regulator of G protein signaling，RGS）在G蛋白偶联受体（G protein coupled receptor，GPCR）信号转导中起着关键作用。RGS蛋白的特征性标志是保守的120-aa RGS区域，其赋予这些蛋白作为G蛋白的GTP酶激活蛋白（GAP）的能力。大多数RGS蛋白可以作为G的多种亚型的GAP，因此有可能影响许多细胞信号通路。然而，RGS蛋白可以被高度调节，并且可以对特定的信号传导途径表现出极端的特异性。RGS蛋白可以通过改变其GAP活性或亚细胞定位来调节;这种调节通过磷酸化、棕榈酰化以及与蛋白质和脂质结合伴侣的相互作用来实现。许多RGS蛋白具有影响GPCR和非GPCR介导的信号传导的GAP非依赖性功能，例如效应物调节或作为效应物的作用。因此，RGS蛋白应该被认为是多功能的信号调节剂。GPCR介导的信号传导对于心血管系统的正常功能至关重要，并且目前是药物治疗疾病的主要靶标。RGS蛋白水平的改变，特别是RGS 2和RGS 4，产生心血管表型。因此，由于GPCR信号通路的重要性和RGS蛋白对这些通路的深刻影响，RGS蛋白是心血管生理学的调节剂，也是潜在的新型药物靶点。(Circ Res. 2005;96：401-411）。
Regulator of G-protein–signaling (RGS) proteins play a key role in the regulation of G-protein–coupled receptor (GPCR) signaling. The characteristic hallmark of RGS proteins is a conserved 120-aa RGS region that confers on these proteins the ability to serve as GTPase-activating proteins (GAPs) for G proteins. Most RGS proteins can serve as GAPs for multiple isoforms of G and therefore have the potential to influence many cellular signaling pathways. However, RGS proteins can be highly regulated and can demonstrate extreme specificity for a particular signaling pathway. RGS proteins can be regulated by altering their GAP activity or subcellular localization; such regulation is achieved by phosphorylation, palmitoylation, and interaction with protein and lipid-binding partners. Many RGS proteins have GAP-independent functions that influence GPCR and non-GPCR–mediated signaling, such as effector regulation or action as an effector. Hence, RGS proteins should be considered multifunctional signaling regulators. GPCR-mediated signaling is critical for normal function in the cardiovascular system and is currently the primary target for the pharmacological treatment of disease. Alterations in RGS protein levels, in particular RGS2 and RGS4, produce cardiovascular phenotypes. Thus, because of the importance of GPCR-signaling pathways and the profound influence of RGS proteins on these pathways, RGS proteins are regulators of cardiovascular physiology and potentially novel drug targets as well. (Circ Res. 2005;96:401-411.)