β-PIX cooperates with GIT1 to regulate endothelial nitric oxide synthase in sinusoidal endothelial cells

Author:

Liu Songling1,Premont Richard T.23ORCID,Park Ki-Hoon1,Rockey Don C.1ORCID

Affiliation:

1. Digestive Disease Research Center, Medical University of South Carolina, Charleston, South Carolina

2. Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio

3. Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio

Abstract

β-PIX is a multidomain protein known to be a GIT1 binding partner. We report here that in the normal liver, the distribution and cellular localization of β-PIX are restricted largely to sinusoidal endothelial cells. Furthermore, β-PIX interacts with eNOS and GIT1 promotes eNOS activity and NO production and therefore exerts a novel posttranslational regulatory function on eNOS activity in sinusoidal endothelial cells. We also have identified specific molecular domains important in GIT1 and β-PIX’s interaction with eNOS, which may represent novel therapeutic targets in the control of sinusoidal blood flow and intrahepatic resistance.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

HHS | NIH | National Institute of General Medical Sciences

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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