Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10196
Title: Regulation of endothelial and myocardial NO synthesis by multi-site eNOS phosphorylation.
Authors: Mount, Peter F;Kemp, Bruce E;Power, David Anthony
Affiliation: Department of Nephrology, Austin Health, Studley Road, Heidelberg 3084, Victoria, Australia. Peter.Mount@nh.org.au
Issue Date: 12-Jul-2006
Citation: Journal of Molecular and Cellular Cardiology 2006; 42(2): 271-9
Abstract: The controlled regulation of nitric oxide (NO) synthesis in endothelial cells and cardiomyocytes by the endothelial form of nitric oxide synthase (eNOS or NOS3) is essential for cardiovascular health. In recent years, a picture of complex and precise regulation of eNOS activity involving multi-site phosphorylation of specific serine and threonine residues has emerged. Regulation of endothelial NO synthesis by multi-site eNOS phosphorylation occurs in response to a wide variety of humoral, mechanical and pharmacological stimuli. This regulation involves numerous kinases and phosphatases, as well as interactions with other aspects of eNOS regulation such as Ca(2+) flux, protein-protein interactions and regulation of subcellular localization. Phosphorylation of eNOS-Ser(1177) close to the carboxy-terminal is a critical requirement for eNOS activation. In addition, phosphorylation of eNOS-Ser(633) in the flavin mononucleotide (FMN) binding domain also increases eNOS activity and appears particularly important for the maintenance of NO synthesis after initial activation by Ca(2+) flux and Ser(1177) phosphorylation. In contrast, NO synthesis is inhibited by phosphorylation of eNOS-Thr(495), which interferes with the binding of calmodulin to the eNOS calmodulin-binding domain. Regulated phosphorylation of eNOS also occurs at eNOS-Ser(114) and eNOS-Ser(615); however, the functions of these phosphorylation sites remain controversial. This review summarizes the present knowledge of the regulation of NO synthesis by multi-site eNOS phosphorylation and its relationship to other mechanisms of eNOS regulation. This progress in understanding important mechanisms controlling endothelial NO synthesis creates new opportunities to understand and potentially treat cardiovascular diseases characterized by deficient NO synthesis.
Internal ID Number: 16839566
URI: http://ahro.austin.org.au/austinjspui/handle/1/10196
DOI: 10.1016/j.yjmcc.2006.05.023
URL: http://www.ncbi.nlm.nih.gov/pubmed/16839566
Type: Journal Article
Subjects: Animals
Cardiovascular Diseases.drug therapy.enzymology
Endothelium, Vascular.enzymology
Humans
Myocardium.enzymology
Nitric Oxide.biosynthesis.deficiency
Nitric Oxide Synthase Type III.metabolism
Phosphorylation.drug effects
Protein Processing, Post-Translational.drug effects
Appears in Collections:Journal articles

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