eNOS phosphorylation in health and disease.

Endothelium plays a fundamental role in maintaining the vascular tone by releasing various biochemical factors that modulate the contractile and relaxatory behavior of the underlying vascular smooth muscle, regulation of inflammation, immunomodulation, platelet aggregation, and thrombosis. Endothelium regulates these cellular processes by activating endothelial nitric oxide synthase (eNOS) responsible for nitric oxide (NO) production. eNOS is constitutively expressed in ECs in response to humoral, mechanical or pharmacological stimulus. eNOS activity is regulated mainly by protein-protein interactions and multisite phosphorylations. The phosphorylation state of specific serine, threonine and tyrosine residues of the enzyme plays a pivotal role in regulation of eNOS activity. Perturbations of eNOS phosphorylation have been reported in a number of diseases thereby emphasizing the importance of regulation of eNOS activity. This review summarizes the mechanism of eNOS regulation through multi-site phosphorylation in different pathologies. Attempts have been made to highlight phosphorylation of eNOS at various residues, regulation of the enzyme activity via posttranslational modifications and its implications on health and disease.