The G protein-coupled receptor kinase (GRK) family consists of seven cytosolic serine/threonine (Ser/Thr) protein kinases, and among them, GRK2 is involved in the regulation of an enormous range of both G protein-coupled receptors (GPCRs) and non-GPCR substrates that participate in or regulate many critical cellular processes. GRK2 dysfunction is associated with multiple diseases, including cancers, brain diseases, cardiovascular and metabolic diseases, and therefore GRK2-specific substrates/inhibitors are needed not only for studies of GRK2-mediated cellular functions but also for GRK2-targeted drug development. Here, we first review the structure, regulation and functions of GRK2, and its synthetic substrates and inhibitors. We then highlight recent work on synthetic peptide substrates/inhibitors as promising tools for fundamental studies of the physiological functions of GRK2, and as candidates for applications in clinical diagnostics.

中文翻译：

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基于G蛋白偶联受体激酶2（GRK2）的磷酸化反应设计底物和抑制剂。

G蛋白偶联受体激酶（GRK）家族由七个胞浆丝氨酸/苏氨酸（Ser / Thr）蛋白激酶组成，其中GRK2参与了两种G蛋白偶联受体（GPCR）的调控以及参与或调节许多关键细胞过程的非GPCR底物。GRK2功能障碍与多种疾病有关，包括癌症，脑病，心血管疾病和代谢性疾病，因此，不仅需要GRK2特异性底物/抑制剂来研究GRK2介导的细胞功能，而且还需要GRK2靶向药物的开发。在这里，我们首先回顾GRK2的结构，调控和功能，及其合成底物和抑制剂。