TY - JOUR
T1 - Design of substrates and inhibitors of G protein-coupled receptor kinase 2 (GRK2) based on its phosphorylation reaction
AU - Kang, Jeong Hun
AU - Toita, Riki
AU - Kawano, Takahito
AU - Murata, Masaharu
AU - Asai, Daisuke
N1 - Funding Information:
We thank Ms. Shigemi Terakubo and Ms. Niño Nakajima (St. Marianna University School of Medicine) for technical support. This work was supported by JSPS KAKENHI grant number 17K08254 and AMED under Grant Number JP19hm0102067.
Publisher Copyright:
© 2020, Springer-Verlag GmbH Austria, part of Springer Nature.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086781575&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086781575&partnerID=8YFLogxK
U2 - 10.1007/s00726-020-02864-x
DO - 10.1007/s00726-020-02864-x
M3 - Review article
C2 - 32577910
AN - SCOPUS:85086781575
SN - 0939-4451
VL - 52
SP - 863
EP - 870
JO - Amino Acids
JF - Amino Acids
IS - 6-7
ER -
