PHLPPs: Emerging players in metabolic disorders.
Drug Discov Today
; 27(10): 103317, 2022 10.
Article
en En
| MEDLINE
| ID: mdl-35835313
ABSTRACT
That reversible protein phosphorylation by kinases and phosphatases occurs in metabolic disorders is well known. Various studies have revealed that a multi-faceted and tightly regulated phosphatase, pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP)-1/2 displays robust effects in cardioprotection, ischaemia/reperfusion (I/R), and vascular remodelling. PHLPP1 promotes foamy macrophage development through ChREBP/AMPK-dependent pathways. Adipocyte-specific loss of PHLPP2 reduces adiposity, improves glucose tolerance,and attenuates fatty liver via the PHLPP2-HSL-PPARα axis. Discoveries of PHLPP1-mediated insulin resistance and pancreatic ß cell death via the PHLPP1/2-Mst1-mTORC1 triangular loop have shed light on its significance in diabetology. PHLPP1 downregulation attenuates diabetic cardiomyopathy (DCM) by restoring PI3K-Akt-mTOR signalling. In this review, we summarise the functional role of, and cellular signalling mediated by, PHLPPs in metabolic tissues and discuss their potential as therapeutic targets.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Fosfoproteínas Fosfatasas
Límite:
Humans
Idioma:
En
Revista:
Drug Discov Today
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2022
Tipo del documento:
Article