1.
Genetic Catalytic Inactivation of GRK5 Impairs Cardiac Function in Mice Via Dysregulated P53 Levels.
JACC Basic Transl Sci
; 7(4): 366-380, 2022 Apr.
Artigo
em Inglês
| MEDLINE
| ID: mdl-35540100
RESUMO
GRK5's catalytic activity in regulating basal and stressed cardiac function has not been studied. Herein, we studied knock-in mice in which GRK5 was mutated to render it catalytically inactive (K215R). At baseline, GRK5-K215R mice showed a marked decline in cardiac function with increased apoptosis and fibrosis. In vitro, restriction of GRK5 inside the nucleus of cardiomyocytes resulted in enhanced cell death along with higher p53 levels. Moreover, in fibroblasts, we demonstrated that K215R mutation promoted the transition into myofibroblast phenotype. This study provides novel insight into the biological actions of GRK5, that are essential for its future targeting.