Design of substrates and inhibitors of G protein-coupled receptor kinase 2 (GRK2) based on its phosphorylation reaction

被引：10
作者：
Kang, Jeong-Hun [1 ]
Toita, Riki [2 ,3 ]
Kawano, Takahito [4 ]
Murata, Masaharu [4 ]
Asai, Daisuke [5 ]
机构：
[1] Natl Cerebral & Cardiovasc Ctr Res Inst, Div Biopharmaceut & Pharmacokinet, 6-1 Shinmachi, Suita, Osaka 5648565, Japan
[2] Natl Inst Adv Ind Sci & Technol, Biomed Res Inst, 1-8-31 Midorigaoka, Ikeda, Osaka 5638577, Japan
[3] Osaka Univ, Adv Photon & Biosensing Open Innovat Lab, AIST, 2-1 Yamadaoka, Suita, Osaka 5650871, Japan
[4] Kyushu Univ, Ctr Adv Med Innovat, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan
[5] St Marianna Univ, Dept Microbiol, Sch Med, Miyamae Ku, 2-16-1 Sugao, Kawasaki, Kanagawa 2168511, Japan
来源：
AMINO ACIDS | 2020年 / 52卷 / 6-7期
关键词：
G protein-coupled receptor kinase; Peptide substrate; Phosphorylation; Inhibitor; Molecular tool; BETA-ARRESTINS; PEPTIDES; COMPLEX; ASSAY; NANOPARTICLES; SELECTIVITY; ACTIVATION; PAROXETINE; EXPRESSION; RHODOPSIN;
D O I：
10.1007/s00726-020-02864-x
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：863 / 870
页数：8
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