文章基本信息

标题：Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands
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作者：David A. Zidar ; Jonathan D. Violin ; Erin J. Whalen 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：24
页码：9649-9654
DOI：10.1073/pnas.0904361106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：CCL19 and CCL21 are endogenous agonists for the seven-transmembrane receptor CCR7. They are equally active in promoting G protein stimulation and chemotaxis. Yet, we find that they result in striking differences in activation of the G protein-coupled receptor kinase (GRK)/{beta}-arrestin system. CCL19 leads to robust CCR7 phosphorylation and {beta}-arrestin2 recruitment catalyzed by both GRK3 and GRK6 whereas CCL21 activates GRK6 alone. This differential GRK activation leads to distinct functional consequences. Although each ligand leads to {beta}-arrestin2 recruitment, only CCL19 leads to redistribution of {beta}-arrestin2-GFP into endocytic vesicles and classical receptor desensitization. In contrast, these agonists are both capable of signaling through GRK6 and {beta}-arrestin2 to ERK kinases. Thus, this mechanism for "ligand bias" whereby endogenous agonists activate different GRK isoforms leads to functionally distinct pools of {beta}-arrestin.
关键词：CCR7 ; CCL19 ; CCL21 ; chemokine ; arrestin