title: Regulation of endothelial nitric oxide synthase activity by protein-protein interaction.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, GA 30912. ysu@gru.edu.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Su
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry / Q000378:metabolism; D034285:Dynamin II / Q000737:chemistry / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000737:chemistry / Q000378:metabolism*; D018272:Porins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000199:Actins; D016632:Apolipoprotein A-I; D002147:Calmodulin; D018841:HSP90 Heat-Shock Proteins; D008075:Lipoproteins, HDL; D018272:Porins; D014404:Tubulin; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D034285:Dynamin II