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题目:: Multi-tasking RGS proteins in the heart: the next therapeutic target?
作者:: Riddle(Evan L),Schwartzman(Raúl A),Bond(Meredith),Insel(Paul A)
状态:: 发布时间2005-03-04 , 更新时间 2007-11-14
期刊:: Circ Res
摘要:: 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 approximately 120-aa RGS region that confers on these proteins the ability to serve as GTPase-activating proteins (GAPs) for G(alpha) proteins. Most RGS proteins can serve as GAPs for multiple isoforms of G(alpha) 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.
语言:: eng
DOI:: 10.1161/01.RES.0000158287.49872.4e

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