G protein coupled receptors as drug targets:: The role of β-arrestins
G protein coupled receptors as drug targets:: The role of β-arrestins
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DOI：
10.2174/187153008783928352
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发表时间：
2008-03-01
影响因子：
1.9
通讯作者：
Pfleger, Kevin D. G.
中科院分区：
文献类型：
--
作者：
Dromey, Jasmin R.;Pfleger, Kevin D. G.
G蛋白偶联受体（gpcr）是非常重要的药物靶点，细胞内支架和衔接蛋白调控其药理学的主要方面。阻滞蛋白与活化的GPCR激酶（GRK）磷酸化受体结合，能够终止G蛋白偶联，将受体内化到网格蛋白包被的囊泡中，并建立独立于G蛋白信号传导的次级信号复合体。这些事件似乎受到GRK磷酸化、泛素化和潜在的抑制蛋白寡聚化的差异调节，这可能是高度依赖受体和细胞类型的。β -阻滞蛋白在从g蛋白依赖信号转变为独立信号的过程中所起的作用，使它们在决定配体结合的下游效应方面处于关键地位。因此，我们必须欣赏这些分子的功能，因为我们努力发现和优化新的GPCR药物治疗内分泌，代谢和免疫疾病。
G protein coupled receptors (GPCRs) are extremely important drug targets and the arrestin intracellular scaffolding and adaptor proteins regulate major aspects of their pharmacology. arrestin binding to activated, GPCR kinase (GRK)-phosphorylated receptors has the capacity to terminate G protein coupling, internalize the receptors into clathrin-coated vesicles and establish a secondary signaling complex independent of G protein signaling. These events appear to be differentially regulated by GRK phosphorylation, ubiquitination and potentially arrestin oligomerization, which are likely to be highly receptor and cell-type dependent. The role of beta-arrestins in switching from G-protein dependent to independent signaling places them in a pivotal position to dictate the downstream effects of ligand binding. Consequently, we must appreciate the functioning of these molecules as we strive to discover and optimize new GPCR drug therapies for endocrine, metabolic and immune disorders.