ArticleThe Journal of biological chemistry2009
Effects of combined phosphorylation at Ser-617 and Ser-1179 in endothelial nitric-oxide synthase on EC50(Ca2+) values for calmodulin binding and enzyme activation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Glutamine Substitution at LysineACS omega · 2026Article
- Promotion of nitric oxide production: mechanisms, strategies, and possibilities.Frontiers in physiology · 2025Review
- Differential superoxide production in phosphorylated neuronal nitric oxide synthase mu and alpha variants.Journal of inorganic biochemistry · 2024Article
- Simvastatin restores pulmonary endothelial function in the setting of pulmonary over-circulation.Nitric oxide : biology and chemistry · 2024Article
- Endothelial regulation of calmodulin expression and eNOS-calmodulin interaction in vascular smooth muscle.Molecular and cellular biochemistry · 2022Article
- Molecular dynamics study of in silico mutations in the auto-inhibitory loop of human endothelial nitric oxide synthase FMN sub-domain.Journal of molecular modeling · 2021Article
- Specific O-GlcNAc modification at Ser-615 modulates eNOS function.Redox biology · 2020Article
- Tyrosine nitration on calmodulin enhances calcium-dependent association and activation of nitric-oxide synthase.The Journal of biological chemistry · 2020Article
- Reciprocality Between Estrogen Biology and Calcium Signaling in the Cardiovascular System.Frontiers in endocrinology · 2020Review
- Generation and characterization of functional phosphoserine-incorporated neuronal nitric oxide synthase holoenzyme.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
- Exploring the conformations of nitric oxide synthase with fluorescence.Frontiers in bioscience (Landmark edition) · 2018Review
- Molecular and cellular underpinnings of normal and abnormal human placental blood flows.Journal of molecular endocrinology · 2018Review
- Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia.The Journal of endocrinology · 2017Review
- Positive versus negative effects of VEGF165 on Ca2+ signaling and NO production in human endothelial cells.American journal of physiology. Heart and circulatory physiology · 2017Article
- Phosphorylation Controls Endothelial Nitric-oxide Synthase by Regulating Its Conformational Dynamics.The Journal of biological chemistry · 2016Article
- Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1.The Journal of biological chemistry · 2016Article
- Wall stretch and thromboxane A₂ activate NO synthase (eNOS) in pulmonary arterial smooth muscle cells via H₂O₂ and Akt-dependent phosphorylation.Pflugers Archiv : European journal of physiology · 2016Article
- Insulin Induces Relaxation and Decreases Hydrogen Peroxide-Induced Vasoconstriction in Human Placental Vascular Bed in a Mechanism Mediated by Calcium-Activated Potassium Channels and L-Arginine/Nitric Oxide Pathways.Frontiers in physiology · 2016Article
- Solving Kinetic Equations for the Laser Flash Photolysis Experiment on Nitric Oxide Synthases: Effect of Conformational Dynamics on the Interdomain Electron Transfer.The journal of physical chemistry. A · 2015Article
- Changes in Ca2+ Signaling and Nitric Oxide Output by Human Umbilical Vein Endothelium in Diabetic and Gestational Diabetic Pregnancies.Biology of reproduction · 2015Article
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6 authors.
Funding
Abstract
We have investigated the possible biochemical basis for enhancements in NO production in endothelial cells that have been correlated with agonist- or shear stress-evoked phosphorylation at Ser-1179. We have found that a phosphomimetic substitution at Ser-1179 doubles maximal synthase activity, partially disinhibits cytochrome c reductase activity, and lowers the EC(50)(Ca(2+)) values for calmodulin binding and enzyme activation from the control values of 182 +/- 2 and 422 +/- 22 nm to 116 +/- 2 and 300 +/- 10 nm. These are similar to the effects of a phosphomimetic substitution at Ser-617 (Tran, Q. K., Leonard, J., Black, D. J., and Persechini, A. (2008) Biochemistry 47, 7557-7566). Although combining substitutions at Ser-617 and Ser-1179 has no additional effect on maximal synthase activity, cooperativity between the two substitutions completely disinhibits reductase activity and further reduces the EC(50)(Ca(2+)) values for calmodulin binding and enzyme activation to 77 +/- 2 and 130 +/- 5 nm. We have confirmed that specific Akt-catalyzed phosphorylation of Ser-617 and Ser-1179 and phosphomimetic substitutions at these positions have similar functional effects. Changes in the biochemical properties of eNOS produced by combined phosphorylation at Ser-617 and Ser-1179 are predicted to substantially increase synthase activity in cells at a typical basal free Ca(2+) concentration of 50-100 nm.
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