Molecular mechanisms of G protein-coupled receptor signaling: role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization.
Molecular mechanisms of G protein-coupled receptor signaling: role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization.
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发表时间：
1997
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通讯作者：
Jie Zhang;Stephen S. G. Ferguson;L. Barak;M. J. Aber;Bruno Giros;R. J. Lefkowitz;M. G. Caron
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作者：
Jie Zhang;Stephen S. G. Ferguson;L. Barak;M. J. Aber;Bruno Giros;R. J. Lefkowitz;M. G. Caron
G 蛋白偶联受体信号传导的动态调节需要导致激动剂介导的信号的产生、关闭和重建的机制之间的协调平衡。 G 蛋白偶联受体激酶 (GRK) 和视紫红质抑制蛋白不仅介导激动剂依赖性 G 蛋白偶联受体脱敏，而且还启动激活受体的内化（隔离），这是导致受体重新敏化的过程。对β-抑制蛋白功能特异性的研究揭示了G蛋白偶联受体内吞途径的多样性，并表明β-抑制蛋白可能作为专门针对动力依赖性网格蛋白介导的内吞作用的受体的接头。此外，小鼠中GRK2基因的失活导致人们发现了GRK2在心脏发育中意想不到的作用，进一步强调了GRK和视紫红质抑制蛋白的多效性功能。
Dynamic regulation of G protein-coupled receptor signaling demands a coordinated balance between mechanisms leading to the generation, turning off and re-establishment of agonist-mediated signals. G protein-coupled receptor kinases (GRKs) and arrestin proteins not only mediate agonist-dependent G protein-coupled receptor desensitization, but also initiate the internalization (sequestration) of activated receptors, a process leading to receptor resensitization. Studies on the specificity of beta-arrestin functions reveal a multiplicity of G protein-coupled receptor endocytic pathways and suggest that beta-arrestins might serve as adaptors specifically targeting receptors for dynamin-dependent clathrin-mediated endocytosis. Moreover, inactivation of the GRK2 gene in mice has lead to the discovery of an unexpected role of GRK2 in cardiac development, further emphasizing the pleiotropic function of GRKs and arrestins.