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Regulation of Endothelial Nitric Oxide Synthase Activity by Protein-Protein Interaction

[ Vol. 20 , Issue. 22 ]


Yunchao Su   Pages 3514 - 3520 ( 7 )


Endothelial nitric oxide synthase (eNOS) is expressed in vascular endothelial cells and plays an important role in the regulation of vascular tone, platelet aggregation and angiogenesis. Protein-protein interactions represent an important posttranslational mechanism for eNOS regulation. eNOS has been shown to interact with a variety of regulatory and structural proteins which provide fine tuneup of eNOS activity and eNOS protein trafficking between plasma membrane and intracellular membranes in a number of physiological and pathophysiological processes. eNOS interacts with calmodulin, heat shock protein 90 (Hsp90), dynamin-2, β-actin, tubulin, porin, high-density lipoprotein (HDL) and apolipoprotein AI (ApoAI), resulting in increases in eNOS activity. The negative eNOS interacting proteins include caveolin, G protein-coupled receptors (GPCR), nitric oxide synthase-interacting protein (NOSIP), and nitric oxide synthase trafficking inducer (NOSTRIN). Dynamin-2, NOSIP, NOSTRIN, and cytoskeleton are also involved in eNOS trafficking in endothelial cells. In addition, eNOS associations with cationic amino acid transporter-1 (CAT-1), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and soluble guanylate cyclase (sGC) facilitate directed delivery of substrate (L-arginine) to eNOS and optimizing NO production and NO action on its target. Regulation of eNOS by protein-protein interactions would provide potential targets for pharmacological interventions in NO-compromised cardiovascular diseases.


Endothelium, Nitric oxide, Protein interactions.


Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, 1120 15<sup>th</sup> Street, Augusta, GA 30912.

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