Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature Medicine 11, 952 - 958 (2005)
Published online: 4 September 2005 | doi:10.1038/nm1289
A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension
Songling Liu1,2,4, Richard T Premont2, Christopher D Kontos2,3, Shoukang Zhu2 & Don C Rockey1,2,4
Abstract
Nitric oxide (NO) production by endothelial cell nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. We sought to understand the mechanism underlying defective eNOS function. Phosphorylation of the serine-threonine kinase Akt, which activates eNOS, was substantially reduced in sinusoidal endothelial cells from injured livers. Overexpression of Akt in vivo restored phosphorylation of Akt and production of NO and reduced portal pressure in portal hypertensive rats. We found that Akt physically interacts with G-protein-coupled receptor kinase-2 (GRK2), and that this interaction inhibits Akt activity. Furthermore, GRK2 expression increased in sinusoidal endothelial cells from portal hypertensive rats and knockdown of GRK2 restored Akt phosphorylation and NO production, and normalized portal pressure. Finally, after liver injury, GRK2-deficient mice developed less severe portal hypertension than control mice. Thus, an important mechanism underlying impaired activity of eNOS in injured sinusoidal endothelial cells is defective phosphorylation of Akt caused by overexpression of GRK2 after injury.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteinsNature Immunology Article (01 Jun 2001)
Is the nitric oxide system involved in genetic hypertension in Dahl rats?Kidney International Original Article
The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.Nature Medicine Article (01 Sep 2000)
See all 36 matches for Research