PHLPPs: Emerging players in metabolic disorders 

 -  Drug Discovery Today, 27(10), p.1-11, 2022 .
<br/><br/> 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-PPAR? axis. Discoveries of PHLPP1-mediated insulin resistance and pancreatic ? 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. 
<br/><br/><label>Subjects--Topical Terms: </label><br/>PHLPP1<br/>PHLPP2<br/>TYPE 2 DIABETES<br/>CARDIOVASCULAR DYSFUNCTION<br/>ATHEROSCLEROSIS